Reseazrhof cell surface aminopeptidase function and translational in chemomcistance of gynecologic cancer

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In this study, we investigated whether P-LAP/IRAP alters the expression of apoptosis regulatory proteins as a mechanism of drug resistance. We transfected P-LAP/IRAP cDNA into endometrial adenocarcinoma cell line (A-MEC), andA-MEC-LAP cells displayed a 1.8-fold, 2.0-fold, and 1.7-fold increase in I050 against paclitaxel, carboplatin, and cisplatin respectively. While treatment of A-MEC-pc cells with carboplatin showed a much stronger PARP cleavage, comparable to the increase observed in cleaved caspases, A-MEC-LAP cells did not show any expression of cleaved PARR These results suggest that P-LAP/IRAP reduces sensitivity to anticancer drugs via inhibition of mitochondria-mediated apoptosis, and may be a molecular target for conquering anticancer drug resistance. Furthermore, we examined whether the malignant potential of endometrial cancer enhanced by P-LAP/IRAP is due to increased glucose uptake via the P-LAP/IRAP-mediated activation of insulin signaling. A-MEC-LAP cells expressed a remarkably high level of GLUT4 proteins. 311-2-deoxyglucose uptake which responds to insulin in A-MEC-LAP cells was significantly higher than that of A-MEC-pc cells. P-LAP/IRAP was involved in the increasing malignant potential of endometrial cancer mediated by insulin. P-LAP/IRAP was suggested to be a potential new target of molecular-targeted therapy for endometrial cancer.Next, we examined whether APN/CD13 alters the expression of apoptosis regulatory proteins as a mechanism of drug resistance. APN/CD13 inhibitor, bestatin inhibited the paclitaxel resistance in ovarian cancer cells. Bestatin and siRNAof APN/CD13 increased sensitivity to anticancer drugs (paclitaxel) via inhibition of mitochondria-mediated apoptosis. APN/CD13 was suggested to be a potential new target of molecular-targeted therapy for ovarian cancer.