| Literature DB >> 30094102 |
Ronggao Chen1,2, Qiyang Cheng1,2, Kwabena Gyabaah Owusu-Ansah1,2, Jun Chen1,2, Guangyuan Song1,2, Haiyang Xie1,2,3,4,5, Lin Zhou1,2,3,4,5, Xiao Xu1,2,3,4,5, Donghai Jiang1,2,3,4,5, Shusen Zheng1,2,3,4,5.
Abstract
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.Entities:
Keywords: Hepatocellular carcinoma; P-gp; acquired resistance; cabazitaxel; sorafenib
Year: 2018 PMID： 30094102 PMCID： PMC6079161
Source DB: PubMed Journal: Am J Cancer Res ISSN： 2156-6976 Impact factor: 6.166