Sandeep Sheth (Larkin U):

Targeting IGF-1-mediated signaling crosstalk to inhibit prostate cancer growth and metastasis

Prostate cancer (PC) is the most prevalent cancer in American men with unknown etiology. STAT3 and Akt pathways are two distinct signaling pathways and both are implicated in the growth of PC. In this study, we examined whether IGF-1, a growth factor whose levels are elevated in PC, could facilitate crosstalk between STAT3 and Akt signaling pathways to advance PC growth. To this end, our Western blot results showed that acute IGF-1 treatment of DU145 cells increased the phosphorylation of Akt, which correlated with the activation of STAT3. These effects of IGF-1 were through activation of IGF-1R, as siRNA-mediated knockdown of IGF-1R attenuated STAT3 activation and Akt phosphorylation. Furthermore, we show that effects of IGF-1 were completely attenuated by resveratrol, a polyphenolic antioxidant commonly found in grapes. Thus, targeted inhibition of IGF-1-induced signaling pathways by resveratrol holds the promise for the development of novel therapeutic agents against PC.