Bag-1L is a Stress-withstand Molecule Prevents the Downregulation of Mcl-1 and c-Raf Under Control of Heat Shock Proteins in Cisplatin Treated HeLa Cervix Cancer Cells

摘要

Background: Cisplatin, a DNA damaging agent, induces apoptosis through increasing DNA fragmentation.However, identification of intrinsic resistance molecules against Cisplatin is vital to estimate the success of therapy.Bag-1 (Bcl-2-associated anthanogene) is one anti-apoptotic protein involved in drug resistance impacting ontherapeutic efficiency. Elevated levels of this protein are related with increase cell proliferation rates, motilityand also cancer development. For this reason, we aimed to understand the role of Bag-1 expression in Cisplatininducedapoptosis in HeLa cervix cancer cells. Cisplatin decreased cell viability in time- and dose-dependentmanner in wt and Bag-1L+HeLa cells. Although, 10μM Cisplatin treatment induced cell death within 24h byactivating caspases in wt cells, Bag-1L stable transfection protected cells against Cisplatin treatment. To assess thepotential protective role of Bag-1, we first checked the expression profile of interacting anti-apoptotic partners ofBag-1. We found that forced Bag-1L expression prevented Cisplatin-induced apoptosis through acting on Mcl-1expression, which was reduced after Cisplatin treatment in wt HeLa cells. This mechanism was also supportedby the regulation of heat shock protein (Hsp) family members, Hsp90 and Hsp40, which were involved in theregulation Bag-1 interactome including several anti-apoptotic Bcl-2 family members and c-Raf.