Stattic enhances the anti-proliferative effect of docetaxel via the Bax/Bcl-2/cyclin B axis in human cancer cells

• Published in: Process biochemistry (1991) Vol. 69; pp. 188 - 196
• Main Authors: Mohammadian, Jamal, Molavi, Ommoleila, Pirouzpanah, Mohammad Bagher, Rahimi, Ali Akbar Rahim, Samadi, Nasser
• Format: Journal Article
• Language: English
• Published: Barking Elsevier Ltd 01.06.2018; Elsevier BV
• Subjects: Annexin V; Anticancer properties; Antiproliferatives; Apoptosis; Bax protein; Bcl-2 protein; Bcl-x protein; Cancer; Cell cycle; Cell growth; Cell proliferation; Cell viability; Combination index; Cyclin B; Docetaxel; Gene expression; Genes; Inhibitors; Lung cancer; Prostate cancer; Proteins; Signal transducer and activator of transcription 3 inhibitor; Staining; Stat3 protein; Stattic; Synergistic effect; Therapy; Transcription; Combination index; Stattic (PubChem CID: 2779853); MTT (PubChem CID: 64965); CI; Docetaxel; Signal transducer and activator of transcription 3 inhibitor; Trypan blue (PubChem CID: 5479131); DAPI; Cell viability; MTT; Docetaxel (PubChem CID: 44408087); FITC; FBS; RT-PCR; PI; Thiazolyl Blue Tetrazolium Bromide; Dimethyl Sulfoxide (PubChem CID: 21584481); RPMI; Stattic; Apoptosis
• ISSN: 1359-5113; 1873-3298
• DOI: 10.1016/j.procbio.2018.03.004

[Display omitted] •Stattic enhances the efficacy of docetaxel by changing the cell cycle distribution of DU-145 prostate cancer cells.•Co-treatment of docetaxel and stattic has a strong synergistic effect.•Combination treatment with two agents (stattic and docetaxel) increase apoptotic cell death in comparison to single treatment.•Comparison of single treatment, combinatorial treatment with stattic and docetaxel leads to decreases the expression of key anti-apoptotic genes (Bcl-2, Bcl-xl). We investigated the effects of Stattic, an important signal transducer and activator of transcription 3 (STAT3) inhibitor, on enhancing the anti-proliferative and apoptotic effects of docetaxel in lung A549 and prostate cancer DU145 cells. Cell proliferation, cellular apoptosis and expression of STAT3 target genes were evaluated by DAPI staining, Annexin V/PI staining, cell cycle analysis and Real Time PCR. The anticancer effects of docetaxel and Stattic combination therapy induced synergistic effects in A549 and DU145 cells with combination indices of 0.71 and 0.52, respectively. Annexin V/PI demonstrated that there was a 2-fold increase in the proportion of apoptotic cells in cells treated with docetaxel and Stattic in A549 and DU145 cell lines, compared with control groups. Compared with cells treated with either docetaxel or Stattic alone, the results of the current study identified a significant decrease in the transcript levels of the anti-apoptotic proteins Bcl-2 and Bcl-xl and a marked increase in the level of the pro-apoptotic protein, Bax in cells that underwent combination therapy with docetaxel and Stattic combination (P < 0.05). These results suggest that combination of a STAT3 inhibitor and taxan derivatives may be developed as a promising therapeutic strategy to treat patients with lung and prostate cancer.