Cabazitaxel, a novel chemotherapeutic alternative for drug-resistant hepatocellular carcinoma

The prognosis of advanced hepatocellular carcinoma (HCC) patients remains extremely poor, partially due to the development of acquired resistance to sorafenib and chemotherapy. Cabazitaxel, a semisynthetic taxane, has been approved for the therapy of docetaxel-resistant prostate cancer. However, no studies have been performed on the effect of cabazitaxel on HCC, and whether cabazitaxel remains sensitive in chemotherapy-resistant and sorafenib-resistant HCC cells is not clear. Our results demonstrate that cabazitaxel is highly toxic to HCC cell lines in a time- and dose-dependent manner by inducing G2/M phase arrest and apoptosis in vitro. Cabazitaxel also significantly suppresses HCC tumor growth in vivo. In chemotherapy-resistant HCC cell Huh-TS-48 with P-gp-overexpression, cabazitaxel shows less cross-resistant to other chemotherapeutic agents. The resistance fold of cabazitaxel, doxorubicin, paclitaxel, docetaxel and vinorelbine is 1.53, 8.60, 38.58, 15.53 and 18.06 respectively. Furthermore, sorafenib-resistant HCC cell SK-sora-5 is still sensitive to cabazitaxel. The IC50 values of cabazitaxel after 72 h exposure for parental cell SK-hep-1 and resistant cell SK-sora-5 are 0.84 and 0.73 nM. The results indicate that cabazitaxel is a potential agent to treat HCC after developing chemotherapy resistance caused by overexpression of P-gp and acquired resistance to sorafenib, and might improve prognosis in advanced HCC patients.