Paclitaxel is recommended as a first-line chemotherapeutic agent 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 TXNDC17 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 TXNDC17 was associated with poorer prognostic factors and exhibited shortened survival in 157 ovarian cancer patients. Moreover, paclitaxel exposure induced upregulation of TXNDC17 and BECN1 expression, increase of autophagosome formation, and autophagic flux that conferred cytoprotection for ovarian cancer cells from paclitaxel. TXNDC17 inhibition by siRNA or enforced overexpression by a pcDNA3.1(+)-TXNDC17 plasmid correspondingly decreased or increased the autophagy response and paclitaxel resistance. Additionally, the downregulation of BECN1 by siRNA attenuated the activation of autophagy and cytoprotection from paclitaxel induced by TXNDC17 overexpression in ovarian cancer cells. Thus, our findings suggest that TXNDC17, through participation of BECN1, induces autophagy and consequently results in paclitaxel resistance in ovarian cancer. TXNDC17 may be a potential predictor or target in ovarian cancer therapeutics.

Ovarian and endometrial cancer will be diagnosed in over 63,000 women in 2009, resulting in 22,000 deaths in the USA. Histologic screening, such as pap smears for detection of cervical cancer, is n...

Objective: To evaluate whether prophylactic chemotherapy (P-chem) increased the drug resistance rate of postmolar GTN and whether the first-line chemotherapy should be different from P-chem. Methods: Postmolar GTN received P-Chem was defined as P-Chem group. Postmolar GTN without P-chem was randomly selected as control group according to the ratio of 1:3 (P-chem:control) and matched by age for low risk and high risk GTN separately. Results: Totally 455 low-risk and 32 high-risk postmolar GTN patients were included. WHO risk score, chemotherapy cycles to achieve hCG normalization and resistant rate were similar between P-chem (27 cases) and control (81 cases) group. Among low-risk GTN patients, interval from hydatidiform mole to GTN was significantly longer in P-chem group than control (44 vs 69 days, P = 0.001). Total chemotherapy cycles and resistant rate were similar between low-risk GTN treated with same agent as P-chem (group A) and alternative agent (group B). But group A needed more chemotherapy cycles to achieve hCG normalization than group B. Conclusions: P-chem delayed the time to GTN diagnosis, but didn’t increase risk score or lead to drug resistance of postmolar GTN. Alternative agent different from P-chem had the potential of enhancing chemotherapy response in low- risk postmolar GTN.