Combined Treatment with Stattic and Docetaxel Alters the Bax/Bcl-2 Gene Expression Ratio in Human Prostate Cancer Cells

Abstract

<br /> <span style="font-size: small;">Docetaxel, recognized as a stabilizing microtubule agent, is frequently administrated as a first line treatment for </span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">prostate cancers. Due to high side effects of monotherapy, however, combinations with novel adjuvants have emerged as an alternative strategy in cancer therapy protocols. Here, we investigated the combined effects of stattic and docetaxel on the DU145 prostate cancer cell line. Cytotoxicity was evaluated by MTT assay. To understand molecular mechanisms of stattic action, apoptotic related genes including Bcl-2, Mcl-1, Survivin and Bax were evaluated by real-time RT-PCR. Alteration in the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 genes and Bax/Bcl-2 ratio were investigated via the 2</span></span>^{<span style="font-size: xx-small;">ΔΔCT</span>}<span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">method. The IC</span></span><span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;">50 </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">values for docetaxel and stattic were 3.7 ± 0.9 nM and 4.6±0.8 μM, respectively. Evaluation of key gene expression levels revealed a noticeable decrease in antiapoptotic Bcl-2 and Mcl-1 along with an increase in pro-apoptotic Bax mRNA levels (p<0.05). Our results suggest that combination of a STAT3 inhibitor with doctaxel can be considered as a potent strategy for induction of apoptosis via increasing Bax mRNA expression.</span></span>