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

  • BMC Cancer. 2023 Jan 25;23(1):87. doi: 10.1186/s12885-023-10561-7.
Wenpeng Cai  #  1  2 ,  Yongfang Ma  #  1 ,  Li Song  #  1 ,  Niandie Cao  1 ,  Jiafeng Gao  1 ,  Shuping Zhou  1 ,  Xiaolong Tang  3  4
Affiliations
  • 1. Medical school, Anhui University of Science and Technology, 232001, Huainan, China.
  • 2. Medical School, Anhui University of Science & Technology, Class 8, Grade 18, Clinical Major, 232001, Huainan, China.
  • 3. Medical school, Anhui University of Science and Technology, 232001, Huainan, China. [email protected].
  • 4. Institute of Environment-friendly Materials and Occupational Health of Anhu University of Science and Technology (Wuhu), 241003, Wuhu, China. [email protected].
  • # Contributed equally.
PMID: 36698167 DOI: 10.1186/s12885-023-10561-7
Abstract

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.

Keywords
Hepatocellular carcinoma; Insulin-like growth factor-1; Insulin-like growth factor-1 receptor; PI3K / akt, RAS / raf / ERK; Podophyllotoxin; Sorafenib.
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