Effect of cisplatin-metformin drug combination on GSTP1 mediated apoptosis

Kllng cancer cells by trggerng cellular apoptoss seems to be the prevalent acton mechansm for cancer drugs. Usng substances that targetng the enzymes partcpatng n the apoptotc pathways that trggers the cellular apoptoss can be a useful treatment opton for cancer. GSTP enzyme, ts newly known role as a modulator of cellular survval and death, can be a good proten molecule for cancer studes. Although, csplatn as one of the most potent alkylatng agent that appled wth success n vast majorty of cancers, ts sde effects are stll lmts the usage of ths drug. Concordantly, to overcome the sde effects, producng less toxc and more effectve drug, combnaton treatment optons are popular research topc n recent years. Metformn s one of the natural product used for dabetes. Recent studes showed that metformn can reduce the rsk of gettng cancer even be able to treat t. In ths respect, the am of ths study s to determne the effects of metformn alone and combnaton wth csplatn on apoptoss n androgen ndependent prostate cancer cell lne (PC3). For ths purpose, cells were treated wth ether metformn alone n the range of 1–10 mM, csplatn alone or a combnaton of these two drugs. Cytotoxcty of drugs were determned wth Alamar Blue Assay and IC50 was calculated. The effect of drugs on proten expresson level of GSTP1 was determned by Western blot technque. In order to valdate our results, apoptoss was examned by usng Annexn V-EGFP kt (BoVson Incorporated CA., USA). Csplatn IC50 value was calculated as 30μM for PC3 cell lne. Both alone or combnaton of drugs were nhbted the prolferaton of PC3 cells n a concentraton dependent manner. GSTP1 proten expressons were sgnficantly down regulated (p=0.05) n metformn/csplatn treated cells compared to control groups. In addton to ths, Annexn V-EGFP levels whch was a sgn of apoptoss, were sgnficantly ncreased by drug combnaton. Ths study suggest that metformn and/or csplatn combnaton may decrease the tumour promoton as well as ncrease the apoptoss n PC3 cells. As a result, ths drug combnaton can be usable for treatment for prostate cancer