[The regulation of APGAT4 on the growth and lenvatinib resistance of hepatocellular carcinoma].

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.

Effect of Wnt/ß-catenin signal pathway on of matrix metalloproteinase-7 and vascular endothelial growth factor gene expressions in endometriosis.

PURPOSE: To explore the function of Wnt/ß-catenin signal pathway on promoting the adhesion, invasion, and metastasis of endometriosis tissues by analyzing its effects on the expressions of matrix metalloproteinase-7 (MMP-7) and vascular endothelial growth factor in en- dometriosis. MATERIALS AND METHODS: Endometriosis nude mice models were included. Small RNA interference technology was used to block Wnt/ß-catenin signal pathway. HE staining technique was adopted to observe the difference of pathological morphology among groups. The immunohistochemistry and real-time quantitative PCR were perfonned to analyze the expressions of $-catenin, MMP-7 and VEGF from pro- tein and mRNA levels. RESULTS: Whether the Wnt/ß-catenin signal pathway was blocked or not had little effect on the pathological mor- phology of lesions. The expressions of P-catenin, MMP-7 and VEGF in siRNA group were much lower than those in negative control group and control group (p < 0.05), while there was no statistical significance in the difference of expressions between negative control group and control group (p > 0.05). CONCLUSION: Blocking of Wnt/ß-catenin signal pathway caused the decrease of MMP-7 and VEGF expressions, in- dicating that Wnt/ß-catenin signal pathway plays an important role in the adhesion, invasion, and metastasis of endometriosis tissues.