Abstract 166: Qiliqiangxin Attenuates Doxorubicin-induced Cardiomyopathy via Regulating Autophagy

Abstract

Aims: Doxorubicin-induced cardiomyopathy, as a common complication of cancer chemotherapy, greatly limits the clinical implication of doxorubicin in the treatment of cancer. Our previous clinical trial and animal studies have shown that Qiliqiangxin, a traditional Chinese medication, was protective for adverse cardiac remodeling. This study aimed at determine the therapeutic effect of Qiliqiangxin in mouse doxorubicin-induced cardiomyopathy. Methods and results: Three groups of mice (control, n=6; doxorubicin+saline, n=7; doxorubicin+Qiliqiangxin, n=7) were followed up for 4 weeks. Echocardiography was taken at the end of 4 weeks to evaluate cardiac function. Mice from the doxorubicin+saline group showed reduced ejection fraction (EF) and fractional shortening (FS) as compared with the mice from the control group. Qiliqiangxin could partly restore the reduction of EF and FS in doxorubicin-induced cardiomyopathy mice. Genes related with autophagosome formation (becline1, ATG4, ATG7, LC3) and autophagosome-lysosome fusion (Cathepsin B, Cathepsin D, Cathepsin L) were determined by quantitative reverse transcription polymerase chain reactions (RT-PCRs) in heart samples from mice of the three groups (control, doxorubicin+saline, doxorubicin+Qiliqiangxin) at the end of 4 weeks. All these 7 genes were found to be increased in doxorubicin-induced cardiomyopathy mice, implying doxorubicin may disturb the autophagy flux of mice hearts through promoting autophagosome formation and inhibiting autophagosome-lysosome fusion. Interestingly, the expression of these 7 genes were decreased in the doxorubicin+Qiliqiangxin group, implying that Qiliqiangxin may protect the cardiac function in doxorubicin-treated mice through regulating the autophagy flux of mice hearts. Moreover, autophagy-related proteins LC3 and P62 were determined by western blotting. Qiliqiangxin reversed the increase of LC3II level and the decrease of P62 level in the doxorubicin-treated mice hearts. Conclusion: Qiliqiangxin may protect the cardiac function of doxorubicin-induced heart failure mice through regulating autophagy in the heart. Qiliqiangxin might be a novel drug for doxorubicin-induced cardiomyopathy.