Anti-ENO1 antibody combined with metformin reverses the resistance of human non-small cell lung cancer A549 cells to cetuximab by targeting cancer stem cells
DOI：10.3872/j.issn.1007-385x.2021.03.004
- VernacularTitle:抗ENO1抗体联合二甲双胍通过靶向肿瘤干细胞逆转人非小细胞肺癌A549细胞对西妥昔单抗的抵抗
- Author:
ZHANG Huiwen
1
;
YANG Ting
1
;
YU Zhuoyue
1
;
SUN Lixin
1
;
LIU Jun
1
;
YU Long
1
;
SUN Lichao
1
;
RAN Yuliang
1
Author Information
1. State Key Laboratory of Molecular Oncology, National Cancer Clinical Medical Research Center, National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Publication Type:Journal Article
- Keywords:
cetuximab (CTX);
metformin (MET);
anti-ENO1 antibody;
lung cancer stem cell;
A549 cell;
combination therapy
- From:
Chinese Journal of Cancer Biotherapy
2021;28(3):239-246
- CountryChina
- Language:Chinese
-
Abstract:
[Abstract] Objective: To explore the effect of anti-ENO1 (enolase 1) antibody and metformin (MET) treatment on the proliferation, migration, invasion and stemness of cetuximab (CTX) -resistant non-small cell lung cancer (NSCLC) cells through targeting cancer stem cells and the possible mechanism. Methods: 10 mmol/L MET combined with 40 μg/ml anti-ENO1 antibody was used to treat CTX(35 µg/ml)-resistant NSCLC A549 cells for 4 d, and the effects of combined treatment on A549 cells were detected with proliferation experiment, colony formation assay, migration and invasion experiments and methylcellulose ball formation experiment. In the meanwhile, FCM was used to detect the effects of CTX, MET and anti-ENO1 antibody single-drug treatment as well as the three-drug combination treatment on ALDH+ and CD44+ lung cancer stem cell subsets. Results: CTX combined with MET and anti-ENO1 antibody treatment significantly inhibited the proliferation, migration, invasion and self-renewal capacity of A549 cells. FCM analysis found that MET could significantly inhibit ALDH+ stem cell subpopulations, while anti-ENO1 antibody could significantly inhibit CD44+ stem cell subpopulations, and the three-drug combination treatment could simultaneously suppress ALDH+ and CD44+ stem cell subpopulations. Conclusion: MET and anti-ENO1 antibody respectively target ALDH+ and CD44+ cancer stem cell subsets, and the combined treatment of MET and anti-ENO1 antibody can effectively reverse the resistance of A549 cells to CTX, and thereby more effectively inhibiting stemness, proliferation, metastasis of A549 cells and tumor recurrence.
- Full text:20210304.pdf
