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Antitumor effects of artesunate on human breast carcinoma MCF-7 cells and IGF-IR expression in nude mice xenografts

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Chinese Journal of Cancer Research 2014年第2期26卷 200-207页

作者： Hai-Ying Dong Zhi-Fei Wang Department of Oncology Zhejiang People's Provincial Hospital Department of Hepatobiliary and Pancreatic Surgery Zhejiang People's Provincial Hospital

Purpose： The objective of this study was to investigate the anti-tumor effects and analyze the mechanism of artesunate （ART） action on breast cancer in vivo using tumor transplanted nude mice. Methods： The human breast tumor cell line MCF-7 was transplanted into nude mice, and the animals were treated with various doses of ART alone or in combination with cyclophosphamide （CTX） or normal saline （NS）. The tumor inhibitory effects were observed and compared, and the ultrastructural morphology of the transplanted tumor cells was observed by electron microscopy. The apoptosis rates and cell cycle status were detected by flow cytometry （FCM）. The expression of apoptosis-related proteins p53, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry and IGF-IR was detected by western blot. The expression correlation for these proteins was also analyzed. Results： The tumor inhibition rates in the low dose ART group, high dose ART group, CTX group and combined drug therapy group were （24.39±10.20）%, （40.24±7.02）%, （57.01±5.84）% and （68.29±5.1）%, respectively. The cell cycle was arrested in phase G0/Gt after treatment with ART. The expression of Bcl-2 was significantly reduced, and the expression levels of Bax and Caspase-3 were significantly increased in the ART group compared to the negative control saline group. There was no significant difference detected in p53 expression. The Bcl-2 level was negatively related to Bax and Caspase-3. The western blotting results showed IGF-IR downregulation. Conclusions： ART inhibits the growth of MCF-7 breast tumor cell xenografts in nude mice. The anti-tumor mechanism of ART for human breast carcinoma in nude mice might be correlated with the alteration of apoptosis related protein expression, which may further induce apoptosis and inhibit cell proliferation.

关键词： Artesunate (ART) nude mice anticancer effect cell apoptosis

Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

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World Journal of Gastroenterology 2008年第27期14卷 4377-4382页

作者： Lin Jia Yuan-Yuan Shang Yu-Yuan Li Department of Digestive Diseases Guangzhou Municipal First People's Hospital Guangzhou Medical College Guangzhou 510180 Guangdong Province China

AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 ± 1.55 g) in the mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was n

关键词： Pancreatic carcinoma Mirtazapine Fluoxetine Body weight nude mice Locomotor activity Ethology

Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice

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World Journal of Gastroenterology 2005年第16期11卷 2426-2430页

作者： Min-HuaZheng BoFeng Jian-WenLi Ai-GuoLu Ming-LiangWang Wei-GuoHu Ji-YuanSun Yan-YanHu Jun-JunMa Bao-MingYu DepartmentofGeneralSurgery RuijinHospitalShanghaiMinimallyInvasiveSurgeryCenterShanghaiInstituteofDigestiveSurgeryShanghaiSecondMedicalUniversityShanghai200025China

AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT. METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7* d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay. RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F= 36.80, Pnude mice, and could be a kind of novel treatment modality for human colon cancer. The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.

关键词： Electrochemotherapy Colorectal neoplasm Bleomycin nude mice Anti-tumor immunity

Antitumor Activities and Apoptosis-regulated Mechanisms of Fermented Wheat Germ Extract in the Transplantation Tumor Model of Human HT-29 Cells in nude mice

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Biomedical and Environmental Sciences 2015年第10期28卷 718-727页

作者： ZHANG Jia Yan XIAO Xiang DONG Ying WU Jing ZHOU Xing Hua School of Food and Biological Engineering Jiangsu University

Objective A subcutaneous transplantation tumor model of human HT-29 cells in nude mice was established to evaluate anticarcinogenic activities, and the apoptosis-regulated mechanism effect of aqueous extract of fermented wheat germ with Lactobacillus plantarum dy-1 （LFWGE）. Methods The HT-29 cells were transplanted via subcutaneous injection of 1×10^7cells into the right flank of each nude mouse. Then, nude mice were treated for 30 d with LFWGE （high-dose 2 g/kg/d; low-dose 1 g/kg/d） and for 7 d with 5-fluorouracil （5-FU, 25 mg/kg/d） by gavage and intraperitoneal injection, respectively. An inhibition of tumor growth was observed. Results Tumor volume and weights decreased significantly in both groups of nude mice treated with LFWGE. In addition, the cell apoptosis rate of the LFWGE group （2 g/kg/d, 60.2%＋4.4%; 1 g/kg/d, 58.6%＋6.9%） was significantly higher than that of the control group （11.5%＋1.6%） and 5-FU group （32.1%＋3.5%） as measured by the TUNEL assay. Moreover, the real-time fluorescent quantitative PCR and Western blot method further confirmed these enhancing apoptosis and growth inhibition effects. The involvement of LFWGE in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, Caspase-3, and CyclinD1. Conclusion The results showed that LFWGE could induce subcutaneous transplantation tumor apoptosis in nude mice and could be as a natural nutrient supplements or chemopreventive agent in the treatment of human colon cancer.

关键词： Fermented wheat germ extract nude mice Antitumor Apoptosis Western blot Human HT-29 cells

Functional Mechanism of Resveratrol in Inhabiting Growth of Cells ls174t and Its Mechanism in Subcutaneously Transplanted Tumor of nude mice

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Chemical Research in Chinese Universities 2008年第6期24卷 756-761页

作者： CHEN Jie DONG Xin-shu GUO Xing-gang The Affiliated Tumor Hospital Harbin Medical University Harbin 150040 P. R. China

To explore the functional mechanism of Resveratrol against colon cancer cells ls174t and the growth of colon cancer tissue of tumor-bearing mice, MTT method was used to observe the functions of resveratrol for inhibition against cells ls174t in vitro. Transmission electron microscope was used to observe the cell apoptosis. FCM assay was performed to measure the change of the cell apoptosis rate and of cell cycle. RT-PCR method was used to detect the expressions of bcl-2 and bax mRNA. Western blot method was used to detect the expressions of bcl-2 and bax protein. Ceils ls174t were transplanted subcutaneously to nude mice to observe the effect of resveratrol on the growth of subcutaneously transplanted tumor, RT-PCR method was used to detect the expressions of bcl-2 and bax mRNA in the tumor tissue. Western blot method was used to detect the expressions of bcl-2 and bax protein in the tumor tissue. Resveratrol has an effect of inhibiting proliferation of cells ls174t in vitro（P〈0.01）. It is able to induce the apoptosis of cells ls174t, causing the decrease in the expression of bcl-2 and the increase in the expression of bax. Resveratrol could inhibit the growth of subcutaneously transplanted tumor of nude mice（P〈0.05）, causing the decrease in the expression of bcl-2 and the increase in the expression of bax. Resveratrol can inhibit the growth of cells 174t and the growth of subcutaneously transplanted tumor. The mechanism is possibly related to the induction of the cell apoptosis and the regulation of bcl-2/bax expression.

关键词： Resveratrol Colon cancer Tumor cell Cell apoptosis nude mice

Antitumor Activities and Apoptosis-regulated Mechanisms of Fermented Barley Extract in the Transplantation Tumor Model of Human HT-29 Cells in nude mice

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Biomedical and Environmental Sciences 2017年第1期30卷 10-21页

作者： YAO Fang ZHANG Jia Yan XIAO Xiang DONG Ying ZHOU Xing Hua School of Food and Biological Engineering Jiangsu University Zhenjiang 212013 Jiangsu China Jiangsu Agri-animal Husbandry Vocational College Taizhou 225300 Jiangsu China

Objective A subcutaneous transplantation tumor model of human HT-29 cells was established in nude mice to study the anticarcinogenic activities and apoptosis-regulatory mechanistic effect of aqueous extract of fermented barley with Lactobacillus plantarum dy-1 （LFBE）. Methods HT-29 cells were transplanted via subcutaneous injection of 1 × 107cells into the right flank of each nude mouse. Then, nude mice were treated for 30 days with LFBE （high-dose 2 g·kg-1·d-1; low-dose 1 g·kg-1·d-1） and for 7 days with 5-fluorouracil （5-FU, 25 g·kg-1·d-1） by gavage and intraperitoneal injection, respectively. Results Tumor volume and weight decreased significantly in both groups of nude mice treated with LFBE. In addition, the cell apoptosis rate of the LFBE group was significantly higher than that of the control group and 5-FU groups as measured by the TUNEL assay. Moreover, the real-time fluorescent quantitative PCR and Western blot methods further confirmed these apoptosis-enhancing and growth-inhibiting effects. The involvement of LFBE in inducing apoptosis was confirmed by the expression of Bax, Bcl-2, caspase-3, and cyclin D1. Conclusion The results showed that LFBE could induce subcutaneous transplantation tumor apoptosis in nude mice and could be used as a natural nutrient supplement or chemopreventive agent in the treatment of human colon cancer.

关键词： Fermented barley extract nude mice Antitumor Apoptosis Human HT-29 cells

Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice

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World Journal of Gastroenterology 2006年第24期12卷 3810-3813页

作者： Dao-Ming Liang Jia-Yong Chen Yi Zhang Ping Gan Jie Lin An-Bao Chen Department of Emergency Surgery of the SecondAffiliated Hospital Kunming Medical College Kunming 650101Yunnan Province China

AIM： To study effects of recombinant human growth hormone （rhGH） on growth of a human gastric carcinoma cell in vivo. METHODS： Experimental mice were divided into control group, rhGH group, oxaliplatin （L-OHP） group and rhGH＋L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model was established successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen （PCNA）, Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method. RESULTS： Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%, 58.2%, 65.2% and 59.2% in rhGH＋L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH＋L-OHP group （or L-OHP group ） and control group or rhGH group （P 〈 0.05）, whereas there were no significant differences （P 〉 0.05） between L-OHP group and rhGH＋L-OHP group and between rhGH group and control group. CONCLUSION： rhGH does not accelerate the proliferation of human gastric cancer cell in vivo.

关键词： Human growth hormone Stomach neoplasm nude mice

Angiostatin inhibits pancreatic cancer cell proliferation and growth in nude mice

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World Journal of Gastroenterology 2005年第32期11卷 4992-4996页

作者： Ding-Zhong Yang Jing He Ji-Cheng Zhang Zhuo-Ren Wang Department of Surgery The First Hospital Xi'an Jiaotong University Xi'an 710065 Shaanxi Province China Department of Pharmacology University of Texas Medical Branch Galveston 77555 Texas State USA Department of Surgery Union Hospital Fujian Medical University Fuzhou 350001 Fujian Province China Zhuo-Ren Wang Department of Surgery The First Hospital Xi'an Jiaotong University Xi'an 710065 Shaanxi Province China

AIM: To observe the biologic behavior of pancreatic cancer cells in vitro and in vivo, and to explore the potential value of angiostatin gene therapy for pancreatic ***: The recombinant vector pcDNA3.1(+)-angiostatin was transfected into human pancreatic cancer cells PC-3 with Lipofectamine 2000, and paralleled with the vector and mock control. Angiostatin transcription and protein expression were determined by immunofluorescence and Western blot. The stable cell line was selected by G418. The supernatant was collected to treat endothelial cells. Cell proliferation and growth in vitro were observed under microscope. Cell growth curves were *** troms-fected or untroms-fected cells overexpressing angiostatin vector were implanted subcutaneously into nude mice. The size of tumors was measured, and microvessel density count (MVD) in tumor tissues was assessed by immunohistochemistry with primary ***: After transfected into PC-3 with Lipofectamine 2000 and selected by G418, macroscopic resistant cell clones were formed in the experimental group transfected with pcDNA 3.1(+)-angiostatin and vector control. But untreated cells died in the mock control. Angiostatin protein expression was detected in the experimental group by immunofluorescence and Western-blot. Cell proliferation and growth in vitro in the three groups were observed respectively under microscope. After treatment with supernatant, significant differences were observed in endothelial cell (ECV-304) growth in vitro. The cell proliferation and growth were inhibited. In nude mice model, markedly inhibited tumorigenesis and slowed tumor expansion were observed in the experimental group as compared to controls, which was parallel to the decreased microvessel density in and around tumor ***: Angiostatin does not directly inhibit human pancreatic cancer cell proliferation and growth in vitro,but it inhibits endothelial cell growthin vitro. It exerts the anti-tum

关键词： Angiostatin Pancreatic cancer Endothelial cell nude mice

Change in expression of apoptosis genes after hyperthermia,chemotherapy and radiotherapy in human colon cancer transplanted into nude mice

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World Journal of Gastroenterology 2007年第32期13卷 4365-4371页

作者： Han Liang Hong-Jie Zhan Bao-Gui Wang Yuan Pan Xi-Shan Hao Department of Gastrointestinal Oncological Surgery Tianjin Cancer Hospital Tianjin Medical University Key Laboratory of Cancer Prevention and Therapy Tianjin 300060 China

AIM:To investigate the change in expression of p53 ,Bcl-2 ,and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia,chemotherapy,radiotherapy,thermochemotherapy,thermoradiotherapy and thermochemoradiotherapy. METHODS:Human colon cancer cell line (HT29) was transplanted into the hind limbs of nude mice. Under laboratory simulated conditions of hyperthermia (43℃,60 min),the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches:hyperthermia,chemotherapy,radiotherapy,thermochemotherapy,thermoradiotherapy,and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane,cytoplasm and nuclei of tumor cells of p53,Bcl-2,and Bax after treatment,were observed by immunohistochemistry staining. RESULTS:All of the six treatment modalities down-regulated the expression of p53,Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia,with chemotherapy,and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 ± 0.009 vs 0.155 ± 0.0115,P < 0.01) and Bcl-2 (0.086 ± 0.010 vs 0.026 ± 0.0170,P < 0.01) and up-regulating Bax expression (0.091 ± 0.0013 vs 0.207 ± 0.027,P < 0.01) compared with any single ***:Hyperthermia enhances the effect of radio-and chemotherapy on tumors by changing the expression of apoptosis genes,such as p53,Bcl-2 and Bax.

关键词： Hyperthermia Apoptosis p53 Bcl-2 Bax nude mice Colon cancer Cell line