Synergistic impacts of rifampicin and doxorubicin against thioacetamide-induced hepatocellular carcinoma in rats  

作　　者：Zahraa R.Elshahawy Entsar A.Saad Rana R.El-Sadda 

机构地区：[1]Chemistry Department,Faculty of Science,Damietta University,Damietta,Egypt [2]Gastroenterology Surgical Center,Faculty of Medicine,Mansoura University,Mansoura,Egypt

出　　处：《Liver Research》2023年第4期352-360,共9页肝脏研究（英文）

摘　　要：Background and aims: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).Materials and methods: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.Alphafetoprotein,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.Results: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,SOD,and p53 decreased(P<0.001)and the rest of the measured marker levels increased(P<0.001)in the HCC-bearing rats;after treatment in all groups,all these changes improved toward 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.Conclusions: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.

关 键 词：Hepatocellular carcinoma(HCC) RIFAMPICIN DOXORUBICIN Bcl-2-associated X protein(Bax) CASPASE Protein 53(p53) THIOACETAMIDE 

分 类 号：R735.7[医药卫生—肿瘤]