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Hypaconitine inhibits TGF-β1-induced epithelial–mesenchymal transition and suppresses adhesion,migration,and invasion of lung cancer A549 cells

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Chinese Journal of Natural Medicines 2017年第6期15卷 427-435页

作者： FENG Hai-Tao ZHAO Wen-Wen lu jin-jian WANG Yi-Tao CHEN Xiu-Ping State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of MacaoMacao China

Epithelial-mesenchymal transition(EMT) has been implicated in tumor invasion and metastasis and provides novel strategies for cancer therapy. Hypaconitine(HpA), a diester-diterpenoid alkaloid isolated from the root of the Aconitum species, exhibits anti-inflammatory, analgesic, and especially, cardiotoxic activities. Here, we reported the anti-metastatic potentials of HpA in transforming growth factor-β1(TGF-β1)-induced EMT in lung cancer A549 cells. The cytotoxic effect of HpA was determined by MTT assay. A549 cells were treated with TGF-β1 with or without HpA co-treatment, and the morphological alterations were observed with a microscopy. The expression of E-cadherin, N-cadherin, and NF-κB was determined by both Western blotting and immunofluorescence analyses. The adhesion, migration, and invasion were detected with Matrigel, wound-healing, and transwell assays, respectively. The expression of Snail was determined by Western blotting. The expression of NF-κB p65, IκBα, and p-IκBα in nuclear and cytosolic extracts was assessed by Western blotting. The results showed that low concentration of HpA(lusion, these results showed that HpA inhibited TGF-β1-induced EMT in A549 cells, which was possibly mediated by the inactivation of the NF-κB signaling pathway, providing an evidence for anti-cancer effect of HpA.

关键词： EMT Hypaconitine TGF-β1 NF-κB

Cucurbitacin B suppresses metastasis mediated by reactive oxygen species(ROS) via focal adhesion kinase(FAK) in breast cancer MDA-MB-231 cells

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Chinese Journal of Natural Medicines 2018年第1期16卷 10-19页

作者： luO Wei-Wei ZHAO Wen-Wen lu jin-jian WANG Yi-Tao CHEN Xiu-Ping State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Science University of Macao

Metastasis is responsible for the majority of cancer-related deaths and prevention of metastasis remains a big challenge for cancer therapy. Cucurbitacin B(Cuc B) is a natural triterpenoid with potent anticancer activities while its effect on metastasis remains unclear. In the present study, the inhibitory effect and mechanisms of Cuc B on metastasis were investigated in MDA-MB-231 breast cancer cells. The cells were treated with or without Cuc B, and the cytotoxicity was determined by MTT assay. The effect of Cuc B on metastasis was evaluated with wound healing, transwell, and adhesion assays. Furthermore, the adhesion of cancer cells to endothelial cells was determined. The protein expression was determined by Western blotting. Cuc B(lular reactive oxygen species(ROS) generation, which could be reduced by N-acetyl-l-cysteine(NAC). In addition, NAC pretreatment could reverse Cuc B-induced suppression of migration and adhesion, expression of FAK, but showed no effect on paxillin expression. In summary, Cuc B suppressed ROS-dependent metastasis through FAK pathway in breast cancer MDA-MB-231 cells, demonstrating novel mechanisms for the anticancer effects of Cuc B.

关键词： Cucurbitacin B Metastasis ROS FAK Breast Cancer

Towards a better understanding of the therapeutic potential of Rhizoma Alismatis: A phytochemical and pharmacological review

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中国药理学与毒理学杂志 2016年第10期30卷 1083-1084页

作者： ZHANG Le-le WANG Yi-tao lu jin-jian State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macao

Rhizoma Alismatis(RA),the dried rhizome of Alisma orientalis(Sam.)Juzep,isa widely used traditional herbal medicine popularly known as″Ze Xie″in *** is an important crude herb component of several famous Chinese preparations including Zexie decoction,Liu Wei Di Huang pills,Wu Ling power and so *** has been used to treat various ailments such as dysuria,edema,nephropathy,hypertension,hyperlipidemia and diabetes,etc.A wide range of chemical compounds mainly triterpenes,diterpenes and sesquiterpenes have been isolated from RA,among which the protostane-type triterpenes termed alisols attract the most attention owing to their unique chemical structure and various biological *** extract and active compounds of RAhave been demonstrated to possess a wide spectrum of pharmacological effects which support its clinical use,***,hypoglycemic,hypolipidemic,hepatoprotective,preventing bone loss,anti-inflammatory andantivirus *** our previous studies,we have investigatedthe anti-proliferative activities of terpenoids isolated from RA and their structure-activity *** B 23-acetate was demonstrated to induce G1 phase cell cycle arrest and apoptosis,and inhibit migration and invasion of ovarian cancer *** present paper reviews the up-to-date information concerning the ethnopharmacology,phytochemistry,pharmacology and toxicology of *** information will be helpful for a better understanding of therapeutic potential of RA as wel as the further explorations.

关键词： Rhizoma Alismatis ethnopharmacology phytochemistry pharmacology

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基于干线对的红外与可见光最优图像配准算法

计算机学报 2007年第6期30卷 1014-1021页

作者：高峰文贡坚吕金建国防科学技术大学电子科学与工程学院空间电子信息技术研究所长沙410073 国防科学技术大学电子科学与工程学院ATR重点实验室长沙410073

提出了一种基于干线对的红外与可见光图像配准算法.该算法分4步:首先分别从基准图像和待配准图像中提取干线对,即对图像中满足特定条件的直线进行配对;然后按照一些准则寻找这两幅图像中的干线对所有可能的匹配情况,并组成一个集合;接... 详细信息

提出了一种基于干线对的红外与可见光图像配准算法.该算法分4步:首先分别从基准图像和待配准图像中提取干线对,即对图像中满足特定条件的直线进行配对;然后按照一些准则寻找这两幅图像中的干线对所有可能的匹配情况,并组成一个集合;接着从该集合中寻找这样一个子集,在保证每个干线对最多出现在它的一个元素中的前提下,使得该子集所有元素的相似性测度之和最大且由它确定的配准误差最小,该文采用分支定限法解决了这一优化问题;最后由最优子集中的所有元素得到同名像点集,运用仿射变换模型,实现图像的配准.大量实验表明,文中提出的方法对红外与可见光遥感图像之间的配准是有效的.

关键词：图像配准干线对分支定限法

Protection of Total Flavonoid Fraction from Nervilia fordii on Lipopolysaccharide-induced Acute lung Injury in Rats

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Chinese Herbal Medicines 2012年第4期4卷 287-293页

作者： HUANG Ming-qing XIE You-liang LAI Xiao-ping LIN Ling XU Yin-ji lu jin-jian CHEN Xiu-ping College of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350108China Institute of Drug Research and Development Guangzhou University of Chinese MedicineGuangzhou 510405China Guangdong Provincial Hospital of Traditiona lChinese Medicine Guangzhou 510120China State Key Laboratory of Quality Rese arch in Chinese Medicine University of MacaoMacao 999078China

Objective To investigate the effects of total flavonoid fraction(TFF) from Nervilia fordii on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats,and to explore their protective *** LPS-induced ALI model was established by LPS(5 mg/kg) injection via left cervical *** samples were collected from the cervical artery of all rats at 5 and 6 h after LPS challenge for arterial blood gas test and cytokines measurements,and pulmonary microvascular permeability(PMP),lung wet/dry weight ratio(W/D),and pathological features were *** Phytochemical study showed that the TFF contained 67.3% of flavonoids expressed in rutin and three flavone *** TFF pretreatment(6.24 and 12.48 mg/kg) attenuated the partial arterial pressure of oxygen decline in blood significantly,and decreased the PMP and lung W/D in ALI *** addition,the TFF(6.24 and 12.48 mg/kg) also ameliorated the LPS-induced lung damages including alveolar edema,neutrophils infiltration,alveolar hemorrhage,and thickening of the alveolar ***,the treatment with the TFF(6.24 and 12.48 mg/kg) also down-regulated the levels of pro-inflammatory cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and intercellular adhesion molecule-1(ICAM-1),and up-regulated the level of anti-inflammatory cytokine IL-10 in serum of ALI rats *** These results suggest that the TFF could protect LPS-induced ALI in rats,which may be mediated,at least in part,by adjusting the production of inflammatory cytokines including TNF-α,IL-6,ICAM-1,and IL-10.

关键词： acute lung injury cytokine Nervilia fordii pulmonary microvascular permeability total flavonoid fraction

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青蒿素类化合物抗肿瘤研究进展

中国药理学通报 2010年第6期26卷 818-820页

作者：陆金健浙江中医药大学生命科学学院浙江杭州310053

青蒿素类化合物是一类有效的抗疟疾药物,近年来研究显示该类化合物也具有良好的抗肿瘤作用。其抗肿瘤机制主要包括铁参与的氧化应激反应、阻滞细胞周期、诱导细胞凋亡以及抗新生血管生成等。由于青蒿素类化合物对正常组织细胞毒性小,且... 详细信息

青蒿素类化合物是一类有效的抗疟疾药物,近年来研究显示该类化合物也具有良好的抗肿瘤作用。其抗肿瘤机制主要包括铁参与的氧化应激反应、阻滞细胞周期、诱导细胞凋亡以及抗新生血管生成等。由于青蒿素类化合物对正常组织细胞毒性小,且对多药耐药的肿瘤细胞仍然有效,因此,开发该类化合物作为新型的抗肿瘤药物具有广阔前景。

关键词：青蒿素氧化应激周期阻滞细胞凋亡抗血管新生抗肿瘤

Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells

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Chinese Journal of Natural Medicines 2020年第7期18卷 517-525页

作者： CHEN Yu-Chi HUANG Mu-Yang ZHANG Le-Le FENG Zhe-Ling jianG Xiao-Ming YUAN luo-Wei HUANG Run-Yue LIU Bo YU Hua WANG Yi-Tao CHEN Xiu-Ping LIN Li-Gen lu jin-jian State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China School of Medicine Chengdu UniversityChengdu 610106China The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine) Guangzhou 510120China

Nagilactone E(NLE),a natural product with anticancer activities,is isolated from Podocarpus *** this study,we reported that NLE increased programmed death ligand 1(PD-L1)expressions at both protein and mRNA levels in human lung cancer cells,and enhanced its localization on the cell ***,NLE increased the phosphorylation and expression of cJun,and promoted the localization of c-Jun in the nucleus,while silencing of c-Jun by small interfering RNA(siRNA)reduced NLEinduced *** study showed that NLE activated the c-Jun N-terminal kinases(JNK),the upstream of c-Jun,and its inhibitor SP600125 reversed the NLE-increased ***,NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell *** summary,NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis,which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.

关键词： Programmed death ligand 1 Nagilactone E lung cancer c-Jun JNK

Effects of garcinone E on ovarian cancer cells:endoplasmic reticulum stress,apoptosis,migration and invasion inhibition

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中国药理学与毒理学杂志 2016年第10期30卷 1075-1076页

作者： XU Xiao-huang LI Ting ZHANG Le-le CHEN Xin GUO Xia CHEN Xiu-ping WANG Yi-tao LIN Li-gen lu jin-jian State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macao

OBJECTIVE Garcinone E,a xanthone derivative isolated from mangosteen,has been reported to have cytotoxic *** aim to study the anticancer effects of garcinone E on ovarian cancer *** MTT assay,LDH release assay,Hoechst33342 staining,AnnexinⅤ/PI staining,and JC-1 staining were used to test the antitumor abilities on several ovarian cancer cell lines,and wound-healing assay,transwell assay,and gelatin zymography were carried out to examine the migratory and invasive effects of malignant ovarian cancer HEY *** m RNA transcription and protein expression were evaluated by Western *** Garcinone E treatment significantly inhibited the proliferation and caused cell death on ovarian cancer HEY,A2780 as well as A2780-palicitaxel resistant *** induced endoplasmic reticulum stress in HEY cells and activated IRE signaling pathway,which provided protection on HEY ***,knocking down of IRE-1αby si RNA further activated caspase cascade and caused more cell *** the other hand,garcinone E eliminated migrative ability of HEY cells by reducing the expression of Rho A and Rac,and it blockaded invasion by down-regulating the protein level of MMP-9 and-2,and up-regulating the protein level of TIMP-1 *** E-reduced activities of MMP-9 and-2 were confirmed by gelatin zymography *** Our finding demonstrated that garcinone E exerts anticancer activities by inducing apoptosis,and suppressing migration and invasion on ovarian cancer cells,which demonstrated certain therapeutic potential of garcinone E on ovarian cancer.

关键词： ovarian cancer garcinone E apoptosis metastasis ER stress

Suppression of AOM/DSS-induced colorectal cancer by scutellarin through downregulation of Wnt signaling pathway activity

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中国药理学与毒理学杂志 2021年第10期35卷 739-740页

作者： ZENG Sha ZHAO Hui CHEN Li SUN Qiang REN Shan LIU Mao-lun YANG Han TANG Shun lu jin-jian XU Hai-bo State Key Laboratory of Southwestern Chinese Medicine Resources Department of PharmacologyChengdu University of Traditional Chinese MedicineChengdu 611137China Institute of Chinese Medical Sciences University of MacaoMacaoChina

OBJECTIVE To investigate the therapeutic effect of scutellarin on colitis-associated cancer(CAC)and its underlying mechanism based on Wnt/β-catenin signaling *** The mouse model of CAC was established by azomethane oxide(AOM)and sodium dextran sulfate(DSS),followed by scutellarin treatment,with recording the body weight,diarrhea and *** sacrificing the mice,the colorectal length and colorectal tumor were *** levels of pro-inflammatory factors TNF-αand IL-6 in mice′s sera were measured by the enzyme-linked immunosorbent assay(ELISA).The colorectal lesions were appraised by hematoxylin and eosin(H&E)***β-catenin level in CAC tissues was probed by immunofluorescent *** apoptosis-related genes Bax and Bcl-2,and Wnt signaling pathway-related genesβ-catenin,GSK-3β,TCF4,c-Myc and cyclin D1 were detected by real-time quantitative RT-PCR(RT-qPCR).Finally,Western blotting analysis(WB)was employed to examine the expressions of the apoptosis and Wnt signaling pathway-related *** Scutellarin significantly improved AOM/DSS-caused weight loss,colorectal length shortening,and tumor growth in mice(P<0.01).Meanwhile,colorectal lesions could be substantially alleviated by *** results showed that the levels of pro-inflammatory factors TNF-αand IL-6 were drastically lessened(P<0.01).Scutellarin also sharply inhibited the nuclear translocation ofβ-catenin,as evidenced by the reduction in the nuclear level ofβ-catenin *** addition,scutellarin attenuated the mRNA expression of Wnt signaling pathway-relatedβ-catenin,TCF4,c-Myc and cyclin D1,whereas it heightened GSK-3βmRNA *** results were consolidated by WB analysis,which indicated that scutellarin could mitigate the protein levels of phospho-GSK-3β,β-catenin,TCF4,c-Myc and cyclin D1,with the increase in GSK-3βprotein in CAC ***,scutellarin could induce the apoptosis of CAC,demonstrated by enhanced expression of Bax and diminished ex

关键词： scutellarin colorectal cancer Wnt signaling pathway AOM/DSS