Effect and Mechanism of FAK Inhibitors on Cytoskeleton Rearrangement， Invasion and Migration of HCC-LM3 Cells
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0106
- VernacularTitle:FAK抑制剂对肝癌HCC-LM3细胞骨架重排和侵袭的作用机制
- Author:
Hong-bing YAO
1
;
Fang XIAO
2
;
Wei GUO
1
;
Jia-xing WU
1
;
Xue-lin WEN
1
;
Jian-hui JIANG
1
;
Yun-peng HUA
3
Author Information
1. Department of Hepatobiliary Surgery， The Second Affiliated Hospital of Guilin Medical University， Guilin 541199，China
2. Department of Oncology， The 924th Hospital of PLA Joint Service Support Force Liuzhou Worker's Hospital， Guilin 541002， China
3. Department of Liver surgery， The First Affiliated Hospital of Sun Yat-sen University， Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
CT-707;
focaladhesionkinase;
hepatic carcinoma;
invasion， migration
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(3):364-372
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect of FAK inhibitor CT-707 on the cytoskeleton rearrangement， invasion and migration of human hepatocellular carcinoma cells HCC-LM3 and its mechanism， and the growth of subcutaneous xenografted tumors in nude mice based on the FAK/PI3K/Akt pathway. MethodsHCC-LM3 cells were divided into Control group， CT-707 low dose （1.5 μmol/L） group， CT-707 medium dose （3 μmol/L） group， CT-707 high dose （6 μmol/L） group. Transwell chamber test， cell scratch， and MTT test were used to determine cell invasion， migration and cell viability. RT-qPCR and Western blot were used to detect the mRNA and protein expression of Palladin， Vimentin， MMP2 and MMP9. Western blot was used to detect the expression of p-FAK， FAK， p-PI3K， PI3K， p-Akt and Akt protein. HCC-LM3 cell line was used to establish subcutaneous xenograft tumor models in nude mice， which were divided into model group and CT-707 group （20 mg/kg， ip）， with 6 mice in each group. The tumor volume and mass were recorded， the tissue structure changes of the transplanted tumor were observed by HE staining method， and the expression of FAK， PI3K， p-Akt， MMP-2， MMP-9 of the transplanted tumor was detected by immunohistochemistry. ResultsCompared with the control group， the CT-707 high， medium and low dose groups could significantly inhibit the invasion and migration ability， decrease cell viability， significantly down-regulate the expression levels of Palladin， Vimentin， MMP2， MMP9， p-FAK/FAK， p-PI3K /PI3K and p-Akt/Akt， （P<0.05）， and the effect of the middle and high-dose groups was significantly better than that of the low-dose group （P<0.05）， and there was no significant difference in the results between the middle and high-dose groups （P>0.05）. Compared with those in the control group， CT-707 could significantly reduce the volume and quality of transplanted tumors and the protein expression of FAK， PI3K， p-Akt， MMP-2， and MMP-9 in the treatment groups （P<0.05）， and the tumor inhibition rate was 51.92%. ConclusionCT-707 may inhibit the invasion and migration of hepatocellular carcinoma cells by inhibiting the activity of FAK/PI3K/Akt signaling pathway， thereby inhibiting cytoskeletal rearrangement and matrix metalloproteinase secretion.
