IGF-1R 通过 PI3K/akt 和 RAS/raf/ERK 信号通路下调肝细胞癌对索拉非尼的敏感性。
IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways.
机构信息
Medical school, Anhui University of Science and Technology, 232001, Huainan, China.
Medical School, Anhui University of Science & Technology, Class 8, Grade 18, Clinical Major, 232001, Huainan, China.
出版信息
BMC Cancer. 2023 Jan 25;23(1):87. doi: 10.1186/s12885-023-10561-7.
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.
背景
胰岛素样生长因子-1 受体 (IGF-1R) 促进细胞增殖、迁移和抑制凋亡，所有这些都可能导致癌症的发展。
方法
本研究探讨了 IGF-1R 在介导肝细胞癌 (HCC) 对索拉非尼耐药中的作用和机制。
结果
IGF-1R 在 HCC 细胞系 SK-Hep1 和 HepG2 中高表达，通过 PI3K/Akt 和 RAS/Raf/ERK 信号通路促进细胞增殖、迁移和抗凋亡，导致 HCC 对索拉非尼耐药。通过 RNA 干扰敲低 IGF-1R 可降低 HCC 细胞的增殖和迁移，并上调索拉非尼诱导的细胞凋亡。体内研究表明，IGF-1R 敲低抑制 SK-Hep1 异种移植物的生长。
结论
这些数据表明，IGF-1R 通过 PI3K/Akt 和 RAS/Raf/ERK 信号通路参与调节 HCC 的存活和细胞生长。干预 IGF-1R 的表达可能会增加索拉非尼对 HCC 的抑制作用。
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