IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways

Background Insulin-like growth factor-1 receptor (IGF-1R) promotes cell proliferation and migration and inhibitsapoptosis, all of which can contribute to the development of cancers. Method This study investigated the effect and mechanism of IGF-1R in mediating the desensitization of hepatocellular carcinoma (HCC) to sorafenib. Results IGF-1R, highly expressed in the HCC cell lines SK-Hep1 and HepG2, promotes cell proliferation, migration, and anti-apoptosis through PI3K / Akt and RAS / Raf / ERK signaling pathways, resulting in HCC resistance to sorafenib. Knockdown of IGF-1R by RNA interference decreased proliferation and cell migration and upregulation of sorafenib-induced apoptosis of HCC cells. In vivo studies demonstrated that IGF-1R knockdown inhibited the growth of SK-Hep1 xenografts. Conclusion These data are evidence that IGF-1R participates in regulating the survival and cell growth of HCC through the PI3K / Akt and RAS / Raf / ERK signaling pathways. Intervention in the expression of IGF-1R may increase the inhibitory effect of sorafenib on HCC.

Automated summary

IGF-1R promotes the proliferation, migration, and anti-apoptosis of HCC cells through the PI3K / Akt and RAS / Raf / ERK signaling pathways, leading to sorafenib resistance. Knockdown of IGF-1R reduces proliferation and migration, and enhances sorafenib-induced apoptosis in HCC cells. In vivo experiments demonstrate that IGF-1R knockdown inhibits the growth of SK-Hep1 xenografts, indicating a role of IGF-1R in regulating HCC survival and cell growth. Intervention in IGF-1R expression may enhance the inhibitory effect of sorafenib on HCC.