Proteasome and HDAC Inhibition Changes the Expression Levels of Bcl-2, Bcl-XL, Bim and Bik Proteins in Androgen-Independent PC-3 Cell Line
AbstractObjective: Prostate cancer is the most common cancer observed and it is estimated to have caused 10% of all cancer-related deaths in men in western countries. Transition from androgen-dependent form to metastatic androgen-independent phase is a consequence of deranged apoptotic response by the cancer cells to therapy. Bcl-2 family members are important modulators of apoptotic response. In this study, we investigated the effects of proteasome and histone deacetylase (HDAC) inhibitor treatment on the expression changes in some Bcl-2 family genes at protein level.Methods: PC-3 cells were cultured in plate before being exposed to different concentrations of unaccompanied bortezomib and TSA as well as bortezomib – TSA combination. After the protein isolation from control and treated cells, whole cell lysate was used for determining Bcl-2, Bcl-XL, Bim and Bik proteins with western blotting method.Results: We observed that after the drug treatment, the expression levels of pro-apoptotic Bim and Bik proteins have increased and those of anti-apoptotic Bcl-2 and Bcl-XL proteins have decreased. Synergy between bortezomib and TSA induces apoptosis.Conclusion: Our results showed that application of low doses of bortezomib and TSA combination may be sufficient for apoptotic response. Our findings may come in handy for the advanced prostate cancer research.
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