持续GP130/STAT3 信号有助于阿霉素，顺铂耐药，和MEK抑制人横纹肌肉瘤细胞.

Title:Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells

Volume: 16 Issue: 7

Author(s): Xiaojuan Wu, Hui Xiao, Ruoning Wang, Lingling Liu, Chenglong Li, Jiayuh Lin

Affiliation:

关键词: STAT3；GP130；横纹肌肉瘤；顺铂；阿霉素；MEK抑制剂。

摘要: To test the role of STAT3 in human rhabdomyosarcoma cells, genetic approaches were used to either knockdown the expression of STAT3 and GP130, an upstream activator of STAT3 using short hairpin RNA (shRNA) or express persistently active STAT3 protein. Knockdown expression of GP130 or STAT3 sensitized cells to anti-cancer drugs doxorubicin, cisplatin, and MEK inhibitor AZD6244. On the other hand, expression of the constitutively active STAT3 protein reduced the sensitivity of rhabdomyosarcoma cells to those drugs.

In addition, we tested a small molecule STAT3 inhibitor LY5 and a GP130 inhibitor bazedoxifene in rhabdomyosarcoma cells. Our data demonstrated that 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 suggested a potentially novel cancer therapeutic strategy using the combination of inhibitors of GP130/STAT3 signaling with doxorubicin, cisplatin, or AZD6244 for rhabdomyosarcoma treatments.

Cite this article as:

Xiaojuan Wu, Hui Xiao, Ruoning Wang, Lingling Liu, Chenglong Li, Jiayuh Lin , Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells, Current Cancer Drug Targets 2016; 16 (7) . https://dx.doi.org/10.2174/1568009615666150916093110