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