Inhibition of Autophagy Enhances Anticancer Effects of Atorvastatin in Cervical Cancer

doi:10.26914/c.cnkihy.2018.030891

科研成果详情

题名	Inhibition of Autophagy Enhances Anticancer Effects of Atorvastatin in Cervical Cancer
作者	Bo Sheng ; Yizuo Song ; Yi Liu ; Fang Xue ; Xueqiong Zhu
发表日期	2018-11-22
会议录名称	2018年浙江省妇科肿瘤学学术年会暨温台妇产科年会论文汇编影响因子和分区
语种	英语
原始文献类型	中国会议
摘要	Background:Statins are the most common cholesterol reduction agents,which also exhibit anticancer effects in several human cancers.However,the underlying mechanisms still remain undefined.Autophagy is a crucial survival mechanism for cancer cells under stress conditions.Thus,this study was conducted to evaluate the potential for atorvastatin to treat cervical cancer and explore whether the anticancer effects could be enhanced in combination with autophagy inhibitors.Methods:To measure cell viability,we performed Cell counting kit 8(CCK 8) assay.We examined apoptosis by flow cytometric assay of apoptosis with Annexin V FITC Staining and western blot using caspase-3,poly(ADP-ribose) polymerase(PARP) and Bim antibodies.To investigate whether atorvastatin inhibited tumor growth in vivo,the nude mice bearing Siha tumor xenografts were given p.o.atorvastatin(50 mg/kg/d) or vehicle for 35 days.To examine autophagy activation,we evaluated the expression of Light Chain 3(LC3) by western blot.Cells were co-treated with atorvastatin and one of two chemical inhibitors:3-methyladenine(3-MA),a class Ⅲ PI3 kinase inhibitor;and bafilomycin-A1(Baf-A1),an inhibitor of the vacuolar type H+-ATPase pump inhibitor that blocks the fusion of autophagosomes and lysosomes.Furthermore,the molecular mechanism by which atorvastatin suppressed cervical cancer cells growth was explored.Results:Atorvastatin inhibited cell proliferation in a dosedependent manner and stimulated apoptosis of cervical cancer cells by inducing caspase 3 and PARP activation and up regulating Bim.The treatment of atorvastatin also suppressed tumor growth in vivo as measured weekly using calipers(P<0.05).In addition,atorvastatin induced the activation of AMP-activated protein kinase(AMPK) and its target raptor,while simultaneously down-regulating activation of Akt.Mammalian target of rapamycin(mTOR),a major AMPK/Akt downstream target and negative autophagy regulator,was also down-regulated by atorvastatin.Atorvastatin administration in Siha and Caski cells increased the expression of LC3-Ⅱ.Pharmacologic inhibition of autophagy significantly enhanced atorvastatin-mediated apoptosis in Siha and Caski cells.Moreover,geranylgeranyl pyrophosphate(GGPP),a downstream lipid isoprenoid intermediate,significantly rescued the effects of atorvastatin mentioned above.Conclusion:In summary,our results show that atorvastatin has pro-apoptotic and autophagy induction activities in cervical cancer both in vitro and in vivo.Moreover,combined treatment with autophagy inhibitors dramatically improves the cytotoxic effects of atorvastatin by promoting apoptotic cell death.The present study provides new insights into alternative therapeutic approaches for cervical cancer therapy via using statins and autophagy inhibition concurrently.
页码	1
DOI	10.26914/c.cnkihy.2018.030891
收录类别	CNKI
引用统计
文献类型	会议论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/167835
专题	第二临床医学院，附属第二医院、育英儿童医院
作者单位	1.Department of Obstetrics and Gynecology 2.the Second Affiliated Hospital of Wenzhou Medical University
推荐引用方式 GB/T 7714	Bo Sheng,Yizuo Song,Yi Liu,et al. Inhibition of Autophagy Enhances Anticancer Effects of Atorvastatin in Cervical Cancer[C],2018:1.