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.
Author(s) Details:-
Min Yao
Research Center of Clinical Medicine, Affiliated
Hospital of Nantong University & Department of Medical Immunology, Medical
College of Nantong University, Nantong 226001, Jiangsu, China.
Wenli Sai
Research Center of Clinical Medicine, Affiliated
Hospital of Nantong University & Department of Medical Immunology, Medical
College of Nantong University, Nantong 226001, Jiangsu, China.
Chunxiu Sha
Research Center of Clinical Medicine, Affiliated
Hospital of Nantong University & Department of Medical Immunology, Medical
College of Nantong University, Nantong 226001, Jiangsu, China.
Min Xu
Research Center of Clinical Medicine, Affiliated
Hospital of Nantong University & Department of Medical Immunology, Medical
College of Nantong University, Nantong 226001, Jiangsu, China.
Rongfei Fang
Department of Gastroenterology, Affiliated
Hospital of Nantong University, Nantong 226001, China.
Li Wang
Research Center for Intelligent Information
Technology, Nantong University, Nantong 226019, China.
Qun Xie
Department of Infectious Diseases, Haian People’s
Hospital, Haian 226600, Jiangsu, China.
Dengfu Yao
Research Center of Clinical Medicine, Affiliated
Hospital of Nantong University & Department of Medical Immunology, Medical
College of Nantong University, Nantong 226001, Jiangsu, China.
Please see the link here:- https://doi.org/10.9734/bpi/nvmms/v9/11781F
