论文部分内容阅读
Paclitaxel is recommended as the first-line chemotherapeutic agents against ovarian cancer,but drug resistance becomes a major limitation of its success clinically.The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear.Here,we showed that TRP14 screened from 356 differentially expressed proteins by LC-MS/MS label-free quantitative proteomics was more highly expressed in paclitaxel resistant ovarian cancer cells and tissues,and the high expression of TRP14 was associated with poorer prognostic factors and exhibited shortened survival in 157 ovarian cancer patients.Moreover,paclitaxel exposure induced upregulation of TRP14 and Beclin1 expression,increase of autophagosome formation and autophagic flux that conferred cytoprotection for ovarian cancer cells from paclitaxel.TRP14 inhibition by siRNA or enforced overexpression by pcDNA3.1(+)-TRP14 plasmid correspondingly decreased or increased autophagy response and paclitaxel resistance,and the abrogation of Beclin1 by siRNA attenuated the activation of autophagy and cytoprotection from paclitaxel induced by TRP14 overexpression in ovarian cancer cells.Thus,our findings suggest that TRP14,via Beclin1 participating,induces autophagy and consequently results in paclitaxel resistance in ovarian cancer.TRP14 may be a potential predictor or target in ovarian cancer therapeutics.