Abstract
Chemoresistance to anticancer drugs is a major obstacle in the efforts to develop a successful treatment strategy for esophageal squamous carcinoma (ESCC). Thus, the exploration of new drugs and treatment strategies for combating resistance are of utmost importance. In this study, we investigated the antitumor drug resistance activity of Jesridonin, a new ent-kaurene diterpenoid, and its possible mechanisms of action using the resistant cancer cell line, EC109/Taxol. MTT assay revealed that Jesridonin had similar IC50 values against EC109 paclitaxel-sensitive cells and drug-resistant EC109/Taxol cells in vitro. In mice, Jesridonin effectively prevented the growth of EC109/Taxol tumor xenografts without exerting any significant toxicity. In addition, Jesridonin significantly inhibited the proliferation of EC109/Taxol cells, induced apoptosis and arrested the cell cycle at the G2/M phase. Furthermore, western blot analysis revealed that Jesridonin upregulated the expression of p53, p53 upregulated modulator of apoptosis (PUMA), cleaved-caspase-9 and cleaved-caspase-3 in EC109/Taxol cells, and downregulated the expression of procaspase-3, procaspase-9 and Bcl-2 in the EC109/Taxol cells in a concentration-dependent manner. Overall, our results demonstrate that Jesridonin may have potential for use in the treatment of paclitaxel-resistant ESCC. The data of the present study may lead to the development of novel treatment strategies for paclitaxel-resistant tumors.