Synergistic Anti-cancer Effect and Mechanism of FZKA Decoction Combined with Gefitinib on A549 Cells
10.13422/j.cnki.syfjx.20192221
- VernacularTitle:扶正抗癌方联合吉非替尼对A549细胞的协同抗癌作用及机制
- Author:
Fang FANG
1
;
Wei SHI
1
;
Xiao-wei JIN
2
;
Wan-yin WU
3
Author Information
1. First Clinical College, Guangxi University of Chinese Medicine, Nanjing 530000, China
2. Yunnan Cancer Hospital, Kunming 650018, China
3. Fangcun Branch of Guangdong Province Hospital of Traditional Chinese Medicine, Guangzhou 510370, China
- Publication Type:Research Article
- Keywords:
Fuzheng Kangai decoction;
Gefitinib;
synergistic effect;
F-box and WD repeat domain-containing(FBW7)/myeloid cell leukemia-1(MCL-1)
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2020;26(4):95-101
- CountryChina
- Language:Chinese
-
Abstract:
Objective::To observe the effect of Fuzheng Kangai (FZKA) decoction combined with gefitinib on the cells proliferation, apoptosis, invasion and metastasis of human lung adenocarcinoma A549 cells in vitro and in vivo, and relevant mechanisms. Method::The A549 cell proliferation of the control group, FZKA decoction groups (0.2, 0.4, 0.8, 1.6, 3.2 g·L-1), Gefitinib groups (10, 20, 40, 60, 80, 100 μmol·L-1) for 24, 48, 72 hours, and FZKA decoction (2 g·L-1) combined with Gefitinib (10 μmol·L-1) groups for 24 hours was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The changes of cell apoptosis, invasion and metastasis abilities of A549 cells were analyzed by flow cytometry, Wound Healing, transwell invasion assay. Western blot assay was used to examine the protein expressions of cleaved Caspase-3, B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-2 associated X (Bax), F-box and WD repeat domain-containing (FBW7) and myeloid cell leukemia-1 (MCL-1) in vitro. Result::Compared with control group, FZKA decoction group and Gefitinib group inhibited the cell proliferation, cell apoptosis, cell invasion and metastasis abilities in a dose-dependent and time-dependent manner, and improve the protein expressions of Bax, Caspase-3, FBW7, but decreased the protein expressions of Bcl-2, MCL-1 (P<0.05). Compared with treatment with Gefitinib alone, FZKA combined with Gefitinib inhibited the proliferation of A549 cells, and induced apoptosis more significantly (P<0.05). Compared with treatment with Gefitinib alone, the cell scratch healing and invasion abilities were significantly reduced after combined treatment (P<0.05). FZKA decoction combined with Gefitinib up-regulated Bax, Caspase-3 and FBW7 protein expressions, and down-regulated Bcl-2 and MCL-1 protein expressions compared with treatment with Gifitinib alone (P<0.05). Conclusion::FZKA decoction combined with Gefitinib can inhibit the proliferation, invasion and metastasis, and induce apoptosis on A549 cells. The mechanism may be associated with the FBW7/MCL-1 pathway.
