Oncogenic Insulin-like Growth Factor-1 Receptor (IGF-1R) As a Promising Targeted-molecule for HCC Therapy

The present study aimed to investigate the clinicopathological features of insulin-like growth factor-1 receptor (IGF-1R) or P-glycoprotein (P-gp) expression in tissues and sera of hepatocellular carcinoma (HCC) patients, further analyze IGF-1R on effects of biological behaviors of HepG2 cells and synergistic role with anti-cancer drugs on reversal MDR of HCC. In HCC, there was an overexpression of the IGF-1R. The connection between IGF-1R activation and the advancement of HCC is still unknown, though. In this work, we looked into how the biological characteristics of HCC cells were affected by IGF-1R editing. The expressions of IGF-1R and P-gp in HCC and their distal non-cancerous tissues (Non-Ca) were analyzed by immunohistochemistry. IGF-1R was edited with CRISPR/Cas9 system, screened specific sgRNAs, and then transfected into HepG2 cells. CCK-8 and scratch wound test detected cell proliferation, migration, invasion, and transwell assays, respectively. Alterations of IGF-1R and P-gp were confirmed by Western blotting. Alterations of anti-cancer drug IC50 values were analyzed at the cell level. The incidences of IGF-1R (93.6%) or P-gp (88.2%) were significantly higher (P<0.001) in the HCC group than those (36.6% in IGF-1R or 26.9% in P-gp) in the Non-Ca group. There was a positive correlation between high IGF-1R and P-gp expression, and they were associated with HBV infection and vascular invasion of HCC. Abnormal levels of serum IGF-1R and P-gp were confirmed and associated with HCC progression. Biological feature alterations of HCC cells transfected with specific sgRNA showed IGF-1R expression down-regulation, cell proliferation inhibition, cell invasion or migration potential decreasing, and enhancing susceptibility of HepG2 cells to anti-cancer drugs. In this study, the specific sgRNA plus anti-tumor drugs had higher inhibitory effects on HCC cells, and the drug IC50 values were significantly decreased with inhibiting cell proliferation of HCC in the sgRNA group, indicating that HCC cells transfected with sgRNA could be more sensitive to anti-cancer drugs via inhibiting the NF-kappa B pathway. These data indicated that the edited oncogenic IGF-1R was useful to inhibit biological behaviors of HCC cells and IGF-1R should be a promising targeted-molecule for HCC therapy.