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Orlistat is an orally administered anti-obesity drug that has shown significantantitumor activity in a variety of tumor cells. To identify the proteins involvedin its antitumor activity, we employed a proteomic approach to reveal proteinexpression changes in the human ovarian cancer cell line SKOV3, following Orlistattreatment. Protein expression profiles were analyzed by 2-dimensional polyacrylamidegel electrophoresis (2-DE) and protein identification was performed on a MALDI-Q-TOFMS/MS instrument. More than 110 differentially expressed proteins were visualizedby 2-DE and Coomassie brilliant blue staining. Furthermore, 71 proteins differentiallyexpressed proteins were positively identified via mass spectrometry (MS)/MS analysis.In particular, PKM1/2, a key enzyme involved in tumorigenesis, was found to besignificantly downregulated in SKOV3 cells following treatment with Orlistat.Moreover, PKM1/2 was proved to be downregulated in SKOV3 cells by western blotanalysis after treatment with Orlistat. Taken together, using proteomic tools,we identified several differentially expressed proteins that underwent Orlistat-inducedapoptosis, particularly PKM2. These changes confirmed our hypothesis that Orlistatis a potential inhibitor of ovarian cancer and can be used as a novel adjuvantantitumor agent.

Orlistat, a novel potent antitumor agent for ovarian cancer: proteomic analysis of ovarian cancer cells treated with Orlistat