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Baicalin extracted from Huangqin(Radix Scutellariae Baicalensis) induces apoptosis in gastric cancer cells by regulating B cell lymphoma(bcl-2)/bcl-2-associated x protein and activating caspase-3 and caspase-9

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Journal of Traditional Chinese Medicine 2017年第2期37卷 229-235页

作者： Wang Hongwei Li Hailong Chen Fengqin Luo Jun Gu Jing Wang Huping Wu Hongyan xu Yan Clinical Laboratory The Hospital Affiliatedto Gansu University of Chinese Medicine Lanzhou 730000China Key Laboratory for Transfer of Dunhuang Medicine atthe Provincial and Ministerial Level Lanzhou 730000 China Department of Teaching and Research of Clinical Laboratory School of Clinical Medicine Gansu Universityof Chinese Medicine Lanzhou 730000 China Clinical Laboratory The Hospital Affiliated to Gansu University of ChineseMedicine Lanzhou 730000 China Key Laboratory for Transfer of Dunhuang Medicine at the Provincial and MinisterialLevel Lanzhou 730000 China Key Laboratoryfor Transfer of Dunhuang Medicine at the Provincia andMinisterial Level Lanzhou 730000 China Gansu Provincial Key Labora-tory of Chinese Medicinal Herbs for Prescription Innovationand Transformation Gansu University of Chinese MedicineLanzhou 730000 China

OBJECTIVE:To evaluate the effects of baicalin in human gastric cancer cells, including apoptosis-inducing effects, and to investigate its underlying mechanisms of ***:Cell proliferation and apoptosis assays were performed to investigate the anti-proliferation effects of baicalin in human gastric cancer BGC-823 and MGC-803 *** time-quantitative polymerase chain reaction and Western blotting analysis were performed to elucidate the molecular mechanisms underlying the anti-tumor properties of ***:In BGC-823 and MGC-803 gastric cancer cells treated with 80, 120, and 160 μmol/L baicalin for 48 h, a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay showed that baicalin significantly inhibited cell proliferation in a dose-dependent manner, while flow cytometric analysis demonstrated that baicalin could induce apoptosis, also in a dose-dependent ***, baicalin up-regulated the expression of caspase-3, caspase-9, and B cell lymphoma(bcl-2)-associated x protein and down-regulated the expression of bcl-2 at both the m RNA and protein ***:Baicalin has potential as a therapeutic agent for gastric cancer by inducing apoptosis in cancer cells.

关键词： Baicalin Stomach neoplasms Apoptosis Lymphoma B-Cell bcl-2-associated x protein Caspases effector

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Effect of Icariin on apoptosis and expression of Fas,Fas ligand,B cell lymphoma,and bcl-2-associated x protein in CD4＋ T lymphocytes from patients with ankylosing spondylitis

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Journal of Traditional Chinese Medicine 2017年第2期37卷 207-213页

作者： Wang Hailong Jiang Quan Feng xinghua Division of Rheumatology Guang'anmenHospital China Academy of Chinese Medical Science Beijing 100053 China Basic Medical School Guiyang University of Chinese Medicine Guiyang 550025 China The SecondAffiliated Hospital Guiyang University of Chinese MedicineGuiyang 550003 China Division of Rheurnatology Guang'anrnen Hospital China Academy of Chinese MedicalScience Beijing 100053 China

OBJECTIVE:To investigate the effects of icariin on apoptosis and the expression of Fas, Fas ligand(Fas L), B cell lymphoma(bcl-2), and bcl-2-associated x protein(Bax) in CD4+ T lymphocytes from patients with ankylosing ***:Primary cultures of peripheral blood CD4+ T lymphocytes were established and treated with icariin at high, medium, and low doses(0.5,0.25, and 0.125 mg/mL).Sulfasalazine treated and helthy cells were used as *** of treated cells was determined by flow *** transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine the effects of icariin on the expression of Fas, Fas L, bcl-2, and *** activity of caspase 8 and caspase 3 was determined by a colorimetric ***:The m RNA and protein expression of Fas,and activity of caspase 8 and caspase 3 in CD4+ T lymphocytes were increased by icariin(P protein expression of bcl-2 was decreased(P xpression of Fas L and Bax were not significantly different between *** proapoptotic effects of icariin were ***:Icariin induces the apoptosis of CD4 + T cells from patients with AS comparing to normal ***, the induction of apoptosis may be the likely mechanism of action of icariin's antirheumatics activities.

关键词： Spondylitis ankylosing Fas Fas Ligand protein Lymphoma B-Cell bcl-2-associated x protein CD4-positive T-lymphocytes Apoptosis Icariin

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Effect of Lichong decoction on expression of bcl-2 and bcl-2-associated x protein mRNAs in hysteromyoma model rat

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Journal of Traditional Chinese Medicine 2013年第2期33卷 238-242页

作者： Donghua Li xin xu Ruiya Qian Jianguo Geng Yan Zhang xiaolei xie Yasong Wang xiaoli Zou School of Traditional Chinese Medicine Capital Medical University Beijing Hospital ofTraditional Chinese Medicine Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing Maternaland Child Health Care Hospital Beijing 100026China

OBJECTIVE:To study on effects of Lichong decoction on expression of apoptosis-controlling genes,bcl-2 and bcl-2-associated x protein(Bax) mRNAs in hysteromyoma tissue of the hysteromyoma model ***:Fifty Wistar female rats were randomly divided into a normal group,a model group,a Lichong decoction group,a Guizifuling capsule group and a Mifepristone *** hysteromyoma rat model was established by intraperitoneal injection of exogenous estrin and *** examination of uterine tissue,uterine coefficient and uterine transverse diameter were made under optic microscope and expressions of bcl-2 and Bax mRNAs in uterine tissue in the groups were detected with real-time fluorescent quantitative polymerase chain reaction(PCR) ***:After treatment,under microscope it was found that in the Lichong decoction group myometrium thinned,muscle fiber slightly overgrowth or long and thin,regular arrangement,inserting phenomenon of inner circular muscle and external longitudinal muscle was occasionally or not seen in the Lichong decoction *** uterine coefficient and the uterine transverse diameter significantly decreased(Pbcl-2 mRNA expression significantly decreased(Px mRNA expression significantly increased in hysteromyoma tissue(Pbcl-2 mRNA expression and increase of Bax mRNA expression.

关键词： Myoma Apoptosis Genes, bcl-2 bcl-2-associated x protein Lichong decoction

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Inhibitory effect of oridonin on proliferation of RPMI8226 cells and the possible underlying mechanism

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Journal of Traditional Chinese Medicine 2016年第2期36卷 225-230页

作者： Hao Yaning Zhao Fei Luo Yuanyuan Zhang Mei Li Shasha Department of Nephrology First Affiliated Hospital of Medical School Xi'an Jiaotong University Department of Hematology First Affiliated Hospital of Medical School Xi'an Jiaotong University Department of Nephrology First Affiliated Hospital of Xi'an Medical University

OBJECTIVE:To observe the effects of oridonin on proliferation and apoptosis of myeloma RPMI8226cells and to investigate the potential underlying ***:RPMI8226 cells were treated with various concentrations of *** proliferation was analyzed using the thiazolyl blue tetrazolium bromide *** was observed by transmission electron ***-V/PI staining and flow cytometry was performed to determine cell *** of apoptosis-related proteins was evaluated by western blot ***:Oridonin suppressed the proliferation of RPMI8226 cells and induced apoptosis in a timeand dose-dependent *** electron microscopy confirmed apoptotic morphologyupon treatment with 20μmol/L oridonin and western blot revealed decreased expressions of the apoptosis suppressors survivin,bcl-2 and pro-caspase-3 proteins,and the increased expression of the apoptosis inducer ***:Our results show that oridonin exhibits an inhibitory effect on the proliferation of RPMI8226 cells and induces *** is associated with altering the balance between bcl-2 and Bax protein expressions and decreased survivin and pro-caspase-3 expressions.

关键词： Oridonin Multiple myeloma Apopto sis Survivin bcl-2-associated x protein Caspase 3

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Effects of erythropoietin on the expression of tumor necrosis factor-alpha and Bax after facial nerve axotomy in rats

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Neural Regeneration Research 2011年第6期6卷 444-449页

作者： Wei Zhang Shengyu Lue Ziying Yu Ming Bi Bin Sun Department of Oral and Maxillofacial Surgery School of Stomatology Jilin University Changchun 130041 Jilin Province China

This study sought to evaluate the effect of high-dose erythropoietin （EPO; 5 000 IU/kg） on the expression of tumor necrosis factor-alpha （TNF-α） and Bax in the facial nucleus after facial nerve transection in rats. A total of 42 Wistar rats of both genders were used in this study, and 40 rats were randomly divided into 2 groups： EPO group and model group. The EPO group was treated with EPO once a day for 5 days at a dose of 5 000 IU/kg body weight. The model group was treated with saline of the same amount. At day 3 after EPO （or saline） treatment, the right facial nerves of the 40 rats were transected at the level of the stylomastoid foramen, with the left sides untreated. The remaining 2 rats that did not undergo axotomy served as the control group. The surviving motor neurons in operated rats were counted in coronal paraffin sections of the facial nucleus. The expression of TNF-a and Bax in the facial nucleus was detected by immunohistochemical staining at days 3, 7, 14, 21, and 28 after axotomy. At days 14, 21, and 28 after facial nerve axotomy, a significantly greater proportion of facial motor neurons survived in the EPO group than in the model group. After axotomy, the expression of TNF-a and Bax increased in motor neurons in both the EPO and the model groups. TNF-o expression reached its peak level at day 14 after axotomy, while Bax expression reached its peak level at day 21. TNF-α expression was much lower in the EPO group than in the model group at all time points. No significant difference in Bax expression was found between the EPO and the model groups. These results indicate that high-dose EPO treatment attenuates the increase in TNF-α expression in the facial nucleus and reduces the loss of motor neurons after facial nerve transection in rats. However, high-dose EPO treatment has little effect on Bax expression.

关键词： erythropoietin tumor necrosis factor-a bcl-2-associated x protein facial motor neuron

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JTE-522-induced apoptosis in human gastric adenocarinoma cell line AGS cells by caspase activation accompanying cytochrome C release,membrane translocation of Bax and loss of mitochondrial membrane potential

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World Journal of Gastroenterology 2002年第2期8卷 217-223页

作者： Hong-Liang Li xiao-Hong Li Jun-Hua Lü xian-Da Ren,Department of Pharmacology,Jinan University Pharmacy College,Guangzhou 510632,Guangdong Province,China Dan-Dan Chen,Department of Cardiology,First Affiliated Hospital,Zhongshan University,Guangzhou 510089,Guangdong Province,China Hai-Wei Zhang,Department of Pathology,Jinan University Medical College,Guangzhou 510632,Guangdong Province,China Cun-Chuan Wang,Department of laparoscopic surgery,First Affiliated Hospital,Jinan University Medical College,Guangzhou 510632,Guangdong Province,China Department of Pharmacology Jinan University Pharmacy College Guangzhou 510632 Guangdong Province China. tsam@***

AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim). METHODS: Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by *** and Z-IETD-CHO. CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.

关键词： Adenocarcinoma Stomach Neoplasms Amino Acid Chloromethyl Ketones Anti-Inflammatory Agents, Non-Steroidal Apoptosis Benzenesulfonates Caspases inhibitors Cyclooxygenase Inhibitors Cysteine proteinase Inhibitors Cytochrome c Group Enzyme Activation Humans In Situ Nick-End Labeling Membrane Potentials Mitochondria Oxazoles Proto-Oncogene proteins Proto-Oncogene proteins c-bcl-2 Research Support, Non-U.S. Gov't Tumor Cells, Cultured bcl-2-associated x protein

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Effect of quercetin on the expression of bcl-2/Bax apoptotic proteins in endometrial cells of lipopolysaccharide-induced-abortion mice

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Journal of Traditional Chinese Medicine 2016年第6期36卷 737-742页

作者： Wang xiaodan Yan Yongping Yang Liu Li Mu Zhong xiuhui Department of Traditional Chinese Veterinary medicine College of Traditional Chinese Veterinary medicine Agricultural University of Hebei Department of Animal Science and VeterinaryMedicine Baoding Vocational and Technical College

OBJECTIVE: To explore the effect of quercetin on the expressions of bcl-2/Bax apoptotic proteins in endometrial cells in mice with abortion induced by ***: For in vivo experiment, twenty five Kunming mice were randomly divided into five groups at day 4 of pregnancy, with 5 mice per group. The mice were treated with lipopolysaccharide(LPS)through tail vein intravenous injection at day 4 of pregnancy, followed by different concentrations of quercetin by oral gavage consecutively at days 5 to6 of pregnancy. On day 7 of gestation, the mice were sacrificed and the histopathological changes of the uterus tissues were observed. Immunohistochemical staining was applied to the detection of bcl-2/Bax apoptotic proteins in the endometrial cells. For in vitro experiment, the primary endometrial cells werecultured using a uterus tissue mass culturing method sampled at day 4.5 of pregnancy. The cells were treated with LPS with or without different dosages of quercetin, respectively, for 12 h after 80% confluence. The expression of bcl-2/Bax apoptotic proteins were detected by western ***: Both the in vivo and in vitro experiments showed decreased expression of bcl-2 and enhanced expression of Bax after LPS treatment, leading to a decreased bcl-2/Bax ratio. The expression of bcl-2 significantly increased while the expression of Bax was significantly elevated, in the LPS plus quercetin group compared to the LPS only ***: These results suggest that quercetin has protective effect by partially regulating the expression of bcl-2/Bax proteins, which in turn inhibits endometrial cell apoptosis and benefits the embryo implantation.

关键词： Quercetin Lipopolysaccharides Abortion,spontaneous Endometrium bcl2 protein,mouse bcl-2-associated x protein

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Alanyl-glutamine dipeptide inhibits hepatic ischemiareperfusion injury in rats

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World Journal of Gastroenterology 2006年第9期12卷 1373-1378页

作者： Chang-Jun Jia Chao-Liu Dai xu Zhang Kai Cui Feng xu Yong-Qing xu Department of Hepatobiliary Surgery Shengjing Hospital China Medical University Shenyang 110004 Liaoning Province China Department of General Surgery Fengtian Hospital Shenyang Medical University Shenyang 110024 Liaoning Province China

AIM： To investigate the protective effect and mechanism of alanyl-glutamine dipeptide （Ala-GIn） against hepatic ischemia-reperfusion injury in rats. METHODS： Rats were divided into group C as normal control Group （/7=16） and group G as alanyl-glutamine pretreatment 07=16）. Rats were intravenously infused with 0.9% saline solution in group C and Ala-GIn -enriched （2% glutamine） 0.9% saline solution in group G via central venous catheter for three days. Then all rats underwent hepatic warm ischemia for 30 min followed by different periods of reperfusion. Changes in biochemical parameters, the content of glutathione （GSH） and the activity of superoxide dismutase （SOD） in liver tissue, bcl-2 and Bax protein expression and morphological changes of liver tissue were compared between both groups. RESULTS： One hour after reperfusion, the levels of liver enzymes in group G were significantly lower than those in group C （P〈0.05）. Twenty-four hours after reperfusion, the levels of liver enzymes in both groups were markedly recovered and the levels of liver enzyme in group G were also significantly lower than those in group C （P〈0.01）. One and 24 h after reperfusion, GSH content in group G was significantly higher than that in group C （P 〈0.05）. There was no statistical difference in activities of SOD between the two groups. One and 24 h after reperfusion, the positive expression rate of bcl-2 protein was higher in group G than in group C （P〈0.05） and the positive expression rate of Bax protein was lower in group G than in group C （P〈0.05）. Histological and ultrastructural changes of liver tissue were inhibited in group C compared to group G. CONCLUSION： Our results suggest that Ala-GIn pretreatment provides the rat liver with significant tolerance to warm ischemia-reperfusion injury, which may be mediated partially by enhancing GSH content and regulating the expression of bcl-2 and Bax proteins in the liver tissue.

关键词： Alanine Transaminase Animals Dipeptides Glutathione Immunohistochemistry L-Lactate Dehydrogenase Liver Male Microscopy, Electron Proto-Oncogene proteins c-bcl-2 Rats Rats, Wistar Reperfusion Injury Superoxide Dismutase bcl-2-associated x protein

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Overexpression of bcl-2 partly inhibits apoptosis of human cervical cancer SiHa cells induced by arsenic trioxide

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Chinese Medical Journal 2000年第1期113卷 84-88页

作者：邓友平林晨郑杰付明梁萧陈洁平肖培根吴旻 Institute of Medicinal Plants CAMS and PUMC Beijing 100094 China Natl. Lab. of Molecular Oncology Department of Cell Biology Cancer Institute Beijing 100021 China Nanjing Railway Medical College Nanjing 210009 China

OBJECTIVE: To study the biological effect of arsenic trioxide (As2O3) on human cervical cancer SiHa cells and SiHa cells overexpressing bcl-2 gene. METHODS: SiHa cells with overexpression of bcl-2 (SiHa-bcl2 cells) were established by transfecting SiHa cells with bcl-2 expression vector. The sensitivities of SiHa and SiHa-bcl2 cells to As2O3 were determined using MTT (Thiazolyl blue) reduction and colony forming ability assay, morphological analysis, flow cytometric analysis, DNA agarose gel electrophoresis, in situ cell death detection (TUNEL), Northern blot, RT-PCR and Western blot. RESULTS: As2O3 inhibited the growth of SiHa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR and Western blot analysis revealed that As2O3 induced SiHa cell apoptosis possibly via inhibiting the expression of HPV16 E7 and decreasing the expression of c-myc. However, we found that SiHa-bcl2 cells partly resisted As2O3 induced apoptosis, which might be related to the prevention of the down-regulation of HPV16 E7 and c-myc gene expression. Nevertheless, As2O3 at a high concentration could still induce apoptosis of SiHa-bcl2 cells mainly via decreasing bcl-2 expression and slightly inhibiting viral gene expression. CONCLUSION: As2O3 is an inducer of the apoptosis of human cervical carcinoma cells and the cells overexpressing bcl-2 can partly resist As2O3 induced apoptosis, but the exact mechanism is unclear.

关键词： Antineoplastic Agents Apoptosis Arsenicals Cell Cycle Cell Survival DNA, Neoplasm Female Humans Oxides Proto-Oncogene proteins Proto-Oncogene proteins c-bcl-2 Tumor Suppressor protein p53 Uterine Cervical Neoplasms bcl-2-associated x protein

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Paclitaxel induces apoptosis in human gastric carcinoma cells

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World Journal of Gastroenterology 2003年第3期9卷 442-445页

作者： Hai-Bo Zhou Ju-Ren Zhu Department Of Gastroenterology, Shandong Provincial Hospital, Jinan 250052, Shandong Province, China Department Of Gastroenterology Shandong Provincial Hospital Jinan 250052 Shandong Province China. zhouhbyy@***

AIM;To investigate the apoptosis in gastric cancer cells induced by paclitaxel,and the relation between this apoptosis and expression of bcl-2 and Bax. METHODS:In in vitro experiments,MTT assay was used to determine the cell growth inhibitory *** electron microscope and TUNEL staining method were used to quantitatively and qualitively detect the apoptosis status of gastric cancer cell line SGC-7901 before and after the paclitaxel *** staining was used to detect the expression of apoptosis-regulated gene bcl-2 and Bax. RESULTS:Paclitaxel inhibited the growth of gastric cancer cell line SGC-7901 in a dose-and time-dependent manner. Paclitaxel induced SGC-7901 cells to undergo apoptosis with typically apoptotic characteristics,including morphological changes of chromatin condensation,chromatin crescent formation,nucleus fragmentation and apoptotic body *** could reduce the expression of apoptosis-regulated gene bcl-2,and improve the expression of apoptosis-regulated gene Bax. CONCLUSION:Paclitaxel is able to induce the apoptosis in gastric *** apoptosis may be mediated by down- expression of apoptosis-regulated gene bcl-2 and up- expression of apoptosis-regulated gene Bax.

关键词： Antineoplastic Agents, Phytogenic Apoptosis Carcinoma Humans Paclitaxel Proto-Oncogene proteins Proto-Oncogene proteins c-bcl-2 Stomach Neoplasms Tumor Cells, Cultured bcl-2-associated x protein

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