Effect of bevacizumab on proliferation and invasion of human lung cancer A549 cells.
- Author:
Di WANG
1
;
Yi HAN
;
Lili ZHU
;
Lili DENG
;
Di QU
;
Feng CUI
;
Yuqing XU
2
Author Information
- Publication Type:Journal Article
- MeSH: Angiogenesis Inhibitors; pharmacology; Bevacizumab; pharmacology; Blotting, Western; Cell Line, Tumor; Cell Movement; Cell Proliferation; drug effects; Enzyme Inhibitors; pharmacology; Humans; Lung Neoplasms; metabolism; pathology; Matrix Metalloproteinase 2; metabolism; Matrix Metalloproteinase 9; metabolism; Neoplasm Invasiveness; Proto-Oncogene Proteins c-met; metabolism; RNA, Messenger; metabolism; Real-Time Polymerase Chain Reaction
- From: Chinese Journal of Oncology 2015;37(8):573-577
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the effect and mechanism of bevacizumab on proliferation and invasion of human lung cancer A549 cells.
METHODSA549 cells were treated with bevacizumab. Proliferation and invasion of the bevacizumab-treated A549 cells were detected using cell counting kit CCK-8 and Transwell assay, respectively. The expression of the mRNA and protein of MMP-2, MMP-9 and c-Met were detected by real-time PCR and Western blotting, respectively.
RESULTSProliferation activity was inhibited at the concentration of 10 µg/ml and promoted at the concentration of 100 µg/ml bevacizumab. Bevacizumab in the concentration of 50 µg/ml had a stronger inhibitory effect on the invasion of A549 cells (16 406.19 ± 5 674.23 penetrated cells) than that of control group (36 108.68 6 263.83, P<0.05). The real-time PCR showed that bevacizumab had a stronger inhibitory effect on the expression of MMP-2 and MMP-9 mRNA at the concentration of 50 µg/ml and on the expression c-Met mRNA at the concentration of 10 µg/ml bevacizumabin the A549 cells. However bevacizumab at the concentration of 100 µg/ml showed a promoting effect on the expression of MMP-2, MMP-9 and c-Met mRNA (1.82 ± 0.31, 1.60 ± 0.25, 2.63 ± 0.48), significantly higher than that of the control group (1.00 ± 0.19, 1.00 ± 0.23, 1.00 ± 0.22, P<0.05). The expression of MMP-2, MMP-9 and c-Met mRNA and protein was inhibited by 10 µg/ml bevacizumab in a time-dependent manner. The Western blot assay showed that bevacizumab had a bi-directional effect on the expression of MMP-2 and c-Met proteins in the A549 cells: a promoting effect at 100 µg/ml and inhibitory effect on the expression of MMP-2 at 50 µg/ml bevacizumab, and inhibitory effect on the expression of c-Met protein at 10 µg/ml bevacizumab.
CONCLUSIONSOur findings indicate that in a certain range of concentrations, bevacizumab has prominent inhibitory effect on the proliferation and invasion of A549 cells. However,over the concentration of 100 µg/ml, bevacizumab shows a weakening anti-invasion effect, even has a promoting effect on cell proliferation. This phenomenon may be related to the inhibiting effect on the expression of MMP-2 and c-Met proteins in a non-concentration-dependent manner by bevacizumab.
