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

• Published in: BMC cancer 2023-01, Vol.23 (1), p.87-87, Article 87
• Main Authors: Cai, Wenpeng, Ma, Yongfang, Song, Li, Cao, Niandie, Gao, Jiafeng, Zhou, Shuping, Tang, Xiaolong
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antibodies; Apoptosis; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell migration; Cell Proliferation; Cell survival; Drug resistance; Experiments; Hepatocellular carcinoma; Humans; Insulin; Insulin-like growth factor I; Insulin-like growth factor-1; Insulin-like growth factor-1 receptor; Insulin-like growth factors; Kinases; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Metastasis; Phosphatidylinositol 3-Kinases - metabolism; PI3K / akt, RAS / raf / ERK; Podophyllotoxin; Proto-Oncogene Proteins c-akt - metabolism; Raf protein; Receptor, IGF Type 1 - metabolism; RNA-mediated interference; Signal Transduction; Sorafenib; Sorafenib - pharmacology; Targeted cancer therapy; Tumors; Xenografts
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-10561-7

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. This study investigated the effect and mechanism of IGF-1R in mediating the desensitization of hepatocellular carcinoma (HCC) to sorafenib. 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. 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.