SRC kinase inhibitor PP2 inhibits invasion and metastasis of lung cancer A549 cells by upregulating connexin43 expression.
10.12122/j.issn.1673-4254.2019.07.08
- Author:
Daoxin WANG
1
;
Yaming LIU
1
;
Wanchen ZHAO
1
;
Ru WANG
1
;
Xuhui TONG
1
;
Guojun JIANG
1
Author Information
1. School of Pharmacy, Bengbu Medical College/Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu 233030, China.
- Publication Type:Journal Article
- Keywords:
PP2;
SRC kinase;
connexin43;
invasion;
lung cancer;
metastasis
- MeSH:
A549 Cells;
Cell Line, Tumor;
Cell Movement;
Cell Proliferation;
Connexin 43;
Humans;
Lung Neoplasms;
Neoplasm Invasiveness;
Protein Kinase Inhibitors;
src-Family Kinases
- From:
Journal of Southern Medical University
2019;39(7):797-803
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of SRC kinase inhibitor PP2 on the invasion and metastasis of lung cancer A549 cells and explore its molecular mechanism.
METHODS:MTT assay was used to evaluate the inhibitory effect of PP2 on the proliferation of A549 cells. Cell scratch and Transwell assays were performed to assess the invasion and metastatic capacity of A549 cells after treatment with 1, 2, 4, 8, and 16 μmol/L PP2 for 24 h. Western blotting was used to detect the expressions of connexin43 (Cx43) and MMP-2 in the cells after small interfering RNA (siRNA)-mediated silencing or overexpression of Cx43; the changes in the cell invasion and metastasis in response to PP2 treatment after Cx43 silencing or overexpression were investigated.
RESULTS:MTT assay showed that treatment with PP2 at 2, 4, 8, 16, and 32 μmol/L significantly inhibited the proliferation of A549 cells in a concentration-dependent manner. Treatments with PP2 at 1, 2, 4, 8, and 16 μmol/L for 24 h also concentration-dependently lowered the invasion and metastatic abilities of the cells ( < 0.05). At 4 and 8 μmol/L, PP2 significantly increased the expression level of Cx43 protein and decreased the expression level of MMP-2 protein. Overexpression of Cx43 significantly enhanced the inhibitory effect of PP2 on the cell invasion and metastasis, and Cx43 silencing significantly attenuated the inhibitory effect of PP2 ( < 0.05).
CONCLUSIONS:PP2 treatment can suppress the invasion and metastasis of A549 cells possibly by modulating the expression of Cx43.
