Persistent GP130/STAT3 signaling contributes to the resistance of doxorubicin, cisplatin, and MEK inhibitor in human rhabdomyosarcoma cells.

Persistent GP130/STAT3 signaling contributes to the resistance of doxorubicin, cisplatin, and MEK inhibitor in human rhabdomyosarcoma cells.
Curr Cancer Drug Targets. 2015 Sep 15;
Authors: Wu X, Xiao H, Wang R, Liu L, Li C, Lin J
Abstract
To examine the role of STAT3 plays in human rhabdomyosarcoma cells, we used genetic approaches to either knockdown the expression of STAT3 and the upstream of STAT3, GP130 using shRNA or express constitutive active STAT3 protein. Knockdown the expression of GP130 or STAT3 sensitized cells to anti-cancer drugs doxorubicin, cisplatin, and MEK inhibitor AZD6244. On the other hand, constitutive active STAT3 decreased the sensitivity of cells to those drugs. Additionally, we tested a novel small molecular STAT3 inhibitor LY5 and a GP130 inhibitor bazedoxifene in rhabdomyosarcoma cells. Our data demonstrated the combination of LY5 or bazedoxifene with doxorubicin, cisplatin, and AZD6244 showed stronger inhibitory effects than single agent alone. In summary, our results demonstrated that GP130/STAT3 signaling contributes to the resistance of these drugs in rhabdomyosarcoma cells. They also implicated a potential cancer therapy strategy with the combination of GP130/STAT3 inhibitor with these drugs in rhabdomyosarcoma cells.
PMID: 26373715 [PubMed - as supplied by publisher]

Source: Current Cancer Drug Targets - September 15, 2015 Category: Cancer & Oncology Authors: Wu X, Xiao H, Wang R, Liu L, Li C, Lin J Tags: Curr Cancer Drug Targets Source Type: research