分割剂量电离辐射对卵巢癌耐药细胞自噬性死亡的影响

目的:研究不同电离辐射方式对卵巢癌耐药细胞株SKVCR自噬性细胞死亡的影响,并探讨其相关机制.方法:实验分为假照组、分割照射组(2 Gy·d-1×5)及单次照射组(10 Gy·d-1×1).采用MTT法检测各组细胞对长春新碱(VCR)、依托泊苷(VP-16)及顺铂(DDP)的药物敏感性,MDC染色及流式细胞术检测自噬发...

Role of fractionated ionizing radiation in autophagy in drug resistance of ovarian cancer

Objective To detect the effects of different subtypes of fractionated ionizing radiation(IR) on autophagy in ovarian cancer cell line and to explore the relevant mechanisms.Methods The cells were divided into control group,fractionated IR group(2 Gy perfraction·d-1×5) and single IR group(10 Gy perfraction·d-1×1).MTT assay was used to detect the drug sensitivities of the cells in three groups to VCR,VP-16 and DDP.MDC staining was used to examine the incidence of autophagy,Real-time fluorescence quantitative PCR was used to detect the expression levels of autophagy-relative genes MAPLC3B and Akt1 mRNA.Western blotting was applied to detect the expressions of autophagy-related protein MAPLC3B,protein kinase B(PKB,Akt1)/mammalian target of rapamycin(mTOR) and its downstream gene P70 S6K.Results Compared with control group,IR increased the drug sensitivities of SKVCR cells to VCR and VP-16,which was more significant in fractionated group(P<0.05).Compared with control group,IR increased the incidence of autophagy,particularly in fractionated IR group.Compared with control group,MAPLC3B was increased and Akt1 was decreased(P<0.05) after irradiation both at mRNA level and protein level,the expressions of mTOR,p-mTOR,P70 S6K,p-P70 S6K were decreased,the changes in fractionated IR group were more significant compared with single IR group.Conclusion Different subtypes of IR can induce the cell death of ovarian cancer,the Akt1/mTOR/S6K signal pathway and autophagy might be involved in the regulation mechanism.