The combination of doxorubicin and rifampicin optimized the effects of the individual drugs, showing the highest selectivity index (3.43) in vitro and exerting the best antioxidant effects in vivo.
Does the combination of rifampicin and doxorubicin improve anti-cancer activity against hepatocellular carcinoma in rats compared to monotherapy?
The combination of rifampicin and doxorubicin demonstrates synergistic anti-cancer and antioxidant effects against thioacetamide-induced hepatocellular carcinoma in a rat model.
p-value: p=<0.001
Combination therapy is a promising new strategy that has been proposed to increase the efficacy of cancer treatment. We aimed to investigate the anti-cancer activity of rifampicin monotherapy and its combination with doxorubicin against hepatocellular carcinoma (HCC). The in vitro half maximal inhibitory concentration (IC50) and selectivity index (SI) of the drugs under investigation against HepG2 and human lung fibroblast (WI38) cell lines were determined. For the in vivo experiment, male Sprague-Dawley albino rats were injected with thioacetamide at 200 mg/kg twice a week for 90 days; HCC development was confirmed histopathologically. Following HCC induction, the rats were treated with intraperitoneal doxorubicin, rifampicin, or their combination for 45 or 90 days. After sacrifice, the livers were examined histopathologically. The levels of aminotransferases, albumin, bilirubin, malondialdehyde, superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and nitric oxide were measured by spectrophotometry. Alpha fetoprotein, cancer antigen 19-9, tumor necrosis factor-alpha, interleukin-6, Bcl-2-associated X protein, caspase 3, caspase 8, and p53 were estimated using ELISA. In vitro, the combination of doxorubicin and rifampicin showed the highest SI of 3.43. In vivo, among the measured markers, the levels of TAC, CAT, and SOD decreased (P < 0.001) and the p53 level increased (P < 0.001) in the HCC-bearing rats; after treatment in all groups, all these changes improved to normal in a time-dependent manner. The combination of doxorubicin and rifampicin optimized the effects of the two individual drugs and exerted the best antioxidant effects. In general, compared with rifampicin or doxorubicin alone, combination therapy has favorable outcomes. Based on our results, the combination of rifampicin and doxorubicin might be applicable for HCC chemotherapy.
Elshahawy et al. (Sat,) conducted a other in Hepatocellular carcinoma. Combination of doxorubicin and rifampicin vs. Doxorubicin alone, rifampicin alone, or untreated was evaluated on Anti-cancer activity (in vitro selectivity index and in vivo antioxidant/apoptotic markers) (p=<0.001). The combination of doxorubicin and rifampicin optimized the effects of the individual drugs, showing the highest selectivity index (3.43) in vitro and exerting the best antioxidant effects in vivo.