目前认为多种抗肿瘤药物能够诱导细胞内质网应激,其活化的未折叠蛋白反应和自噬等细胞应答反应与肿瘤化疗药物耐受密切相关。我们前期工作已经发现：由本课题合作单位大连理工大学开发的BH3-only蛋白模拟物S1可通过抑制抗凋亡蛋白Bcl-2/Mcl-1来诱导卵巢癌顺铂耐药细胞凋亡，并引起了内质网应激和自噬相关蛋白表达的变化。因而我们假设：内质网应激信号通路可能在BH3-only蛋白模拟物诱导的肿瘤细胞凋亡过程中发挥重要作用，Bcl-2可能是耐药细胞应答反应的核心调控因子。本课题拟以BH3-only蛋白模拟物ABT-737为对照，比较S1、ABT-737分别作用于卵巢癌顺铂耐药细胞诱导的内质网应激、自噬及凋亡之间的差异，探讨内质网应激和自噬在S1抗肿瘤过程中的作用；并使用分子生物学与生物信息学等实验方法，进一步明确抗凋亡蛋白Bcl-2调控内质网应激信号网络的机制，为S1逆转肿瘤耐药机制提供理论依据。

A variety of anticancer agents could induce endoplasmic reticulum（ER） stress, and some adaptive responses involved in this process such as unfolded protein response (UPR) and autophagy were thought to be closely related to chemotherapy resistance .The anti-apoptotic protein Bcl-2 not only is related to drug resistance, but also involved in the regulation of endoplasmic reticulum stress signaling networks; however, the molecular link between these two is still not very clear. As studies focusing on the function of Bcl-2 at the level of the ER goes far, the research and development of BH3-only protein mimetics which shows target inhibition of the anti-apoptotic protein Bcl-2 especially provide us with new possibilities. Our experiment aims to comparatively study the effects of the BH3-only protein mimetics S1 and the control group ABT737 on endoplasmic reticulum stress,autophagy and apoptosis in cisplatin- resistant human ovarian cancer cell lines. Experimental protocols in molecular biology and bioinformatics are used to explore the roles for endoplasmic reticulum stress and autophagy in the anti-tumor process of the BH3-only protein mimetics,and to clarify the relevant mechanisms for Bcl-2 regulation of endoplasmic reticulum stress signaling networks, thereby providing certain theoretical and experimental basis for the role of the BH3-only protein mimetics S1 in the reversal of chemo-resistance.