The regulation of APGAT4 on the growth and lenvatinib resistance of hepatocellular carcinoma.
10.3760/cma.j.cn501113-20230225-00080
- VernacularTitle:AGPAT4对肝细胞癌生长和仑伐替尼耐药的调控作用
- Author:
Zhu LI
1
;
Neng Hong YANG
2
;
Bo LI
2
;
Cheng Yi SUN
3
Author Information
1. The Second Affiliated Hospital of Soochow University, Suzhou 215004, China Department of Hepatobiliary Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
2. Department of Hepatobiliary Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
3. The Second Affiliated Hospital of Soochow University, Suzhou 215004, China Guizhou Medical University, Guiyang 550004, China.
- Publication Type:Journal Article
- Keywords:
1-acyl-sn-glycerol-3-phosphate acyltransferaseδ;
Hepatocellular carcinoma;
Lenvatinib resistance;
Tumor growth
- MeSH:
Animals;
Mice;
Carcinoma, Hepatocellular/pathology*;
Liver Neoplasms/pathology*;
Mice, Nude;
Cell Line, Tumor;
Cell Proliferation;
RNA, Messenger;
Gene Expression Regulation, Neoplastic
- From:
Chinese Journal of Hepatology
2023;31(4):408-414
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect of 1-acyl-sn-glycerol-3-phosphate acyltransferaseδ (APGAT4) on the growth and lenvatinib resistance of hepatocellular carcinoma (HCC), and provide novel targets for HCC treatment. Methods: Using the bioinformatics methods to screen out upregulated genes in lenvatinib resistant cell lines from GEO dataset and survival related genes from TCGA dataset. Immumohistochemical staining was used to detect the expression AGPAT4 in HCC tissues, and its correlation with patients' survival. CCK8, EdU, cell cycle, and cell apoptosis assays were used to investigate the impact of role AGPAT4 on the proliferation and lenvatinib reistance of HCC cells. AGPAT4 stable knockdown cell line and subcutaneous nude mouse model were established to test the therapeutic effects of Lenvatinib. Analysis of variance was used to compare the differences between data sets. Results: APGAT4 was the common factor that predicted poor survival and Lenvatinib resistance. The mRNA and protein levels of APGAT4 were significantly upregulated in HCC tissues compared to the para-tumor tissues (P < 0.05). Using siRNA could significantly knocked down the mRNA and protein expression of APGAT4 in HCC cell lines Hep3B and HCCLM3. Compared with the control group, the proliferation ability of HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group was significantly inhibited, and the cell cycle was arrested in G2/M phase (P < 0.05). In addition, compared to the control group, HCC cell lines (Hep3B and HCCLM3) in APGAT4 knockdown group showed significant decrease in the Lenvatinib half maximal inhibitory concentration, and were more sensitive to lenvatinib-induced apoptosis (P < 0.05). In HCC subcutaneous nude mouse model, compared to the control group, the growth of tumor in APGAT4 knockdown group was significantly suppressed, and more apoptosis cells were induced (P < 0.05). Conclusion: APGAT4 promotes the growth and Lenvatinib resistance of HCC, which is a potential target for HCC treatment. Targeting APGAT4 treatment is conducive to inhibit the growth and Lenvatinib resistance of HCC.
