Zahra Samanarad - Department of microbial biotechnology, Islamic Azad University, Tehran North Branch, Tehran, Iran
Abbas AkhavaneSepahy - Department of microbiology-faculty of biology- islamic Azad university -north tehran branch-Tehran -iran
Maryam Bikhof Torbati - Department of Biology, Islamic Azad University, Yadegar-e-Imam Khomeini (RAH) Shahr-e-Rey Branch, Tehran, Iran

Introduction: This study aimed to investigate the synergistic and separate cytotoxicity effects of carboplatin (a chemotherapy medication) and Lactobacillus plantarum cell lysate supernatant (CLS) in the SK-OV-۳ ovarian cancer cell line and the expression change of apoptotic Bax and anti-apoptotic Bcl-۲ genes.Materials and Methods: L. Plantarum CLS at concentrations of ۰.۰۵, ۰.۱, ۰.۱۵, ۰.۲۵, ۰.۵, ۱, ۱.۲۵, and ۱.۵ mg/ml and carboplatin at concentrations of ۰.۱, ۰.۵, ۱, ۲, ۲.۵, ۵, ۱۰, ۲۰, ۴۰, and ۵۰ μg/ml were prepared. Separate and synergistic toxicity effects of carboplatin and L. Plantarum CLS at different concentrations were investigated on the SK-OV-۳ cell line at intervals of ۲۴, ۴۸, and ۷۲ h using the MTT method. Also, the expression level of Bax and Bcl-۲ genes in the treated SK-OV-۳ cell line was analyzed using Real-time PCR.Results: In the current study, the highest increases of toxicities in the separate and synergistic application of carboplatin and L. Plantarum CLS were seen after ۴۸-h treatment against cancer cells. These toxicities were time-dependent, and with increasing time from ۲۴ to ۷۲ h, their cytotoxicity increased. The results of the MTT test showed that drug and probiotics synergism could cause the highest decrease in the survival rate of the SK-OV-۳ cell line in ۷۲, ۴۸, and ۲۴ h, respectively. This synergism led to a ۲.۸-fold decrease in the expression of the Bcl-۲ gene and a ۳.۵-fold increase in the Bax gene compared to the control group. Carboplatin alone decreased Bcl-۲ by ۱.۴ times and increased Bax by ۱.۵ times, and CLS alone decreased Bcl-۲ by ۳.۲ times and increased Bax by ۱.۲ times.Discussion and Conclusion: We concluded the combination of an L. Plantarum CLS (۰.۱ mg/ml) and carboplatin (۰.۵ μg/ml) has induced apoptosis in the SK-OV-۳ cell line. L. plantarum. CLS can be used as adjunctive therapy with carboplatin through increased toxicity and changes in apoptosis gene expressions.

Ovarian cancer, L. Plantarum CLS, Carboplatin, SK-OV-۳, Bcl-۲, BaxBax