Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2112872 | Cancer Letters | 2013 | 7 Pages |
This study evaluated the potential ability of MK-0646 to inhibit IGF1-mediated biological actions and cell signaling events in Type 1 and Type 2 endometrial cancer. We found that MK-0646 treatment significantly decreased IGF1R expression. In addition, pretreatment with MK-0646 decreased the IGF1-induced phosphorylation of IGF1R, AKT and ERK. Apoptosis analyses showed that MK-0646 abolished the anti-apoptotic effect of IGF1. Furthermore, MK-0646 treatment abolished the IGF1-stimulatory effect on proliferation and enhanced the cytotoxic effect of cisplatin. These findings indicate that specific inhibition of IGF1R could be a useful therapeutic approach for Type 1 and Type 2 endometrial cancer.
► MK-0646 treatment significantly decreased IGF1R expression in Type 1 and Type 2 endometrial cancer. ► MK-0646 abolished the anti-apoptotic effect of IGF1 and its stimulatory effect on proliferation. ► MK-0646 enhanced the cytotoxic effect of cisplatin. ► IGF1R targeting could be a useful therapeutic approach for endometrial cancer.