吉非替尼联合二甲双胍对EGFR-TKIs原发性耐药非小细胞肺癌H1975细胞的抑制作用及其机制研究

潘永红; 焦琳; 林采余; 卢从华; 王玉波; 陈恒屹; 李力; 何勇

doi:10.16016/j.1000-5404.201610137

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吉非替尼联合二甲双胍对EGFR-TKIs原发性耐药非小细胞肺癌H1975细胞的抑制作用及其机制研究

更新时间：2026-01-09

- 吉非替尼联合二甲双胍对EGFR-TKIs原发性耐药非小细胞肺癌H1975细胞的抑制作用及其机制研究
- Inhibitory effect and mechanism of gefitinib combined with metformin on EGFR-TKI intrinsic resistant NSCLC H1975 cells
- 第三军医大学学报 2017年39卷第7期页码：668-674
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201610137
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- 收稿：2016-10-23，
  
  纸质出版：2017-07
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潘永红, 焦琳, 林采余, 等. 吉非替尼联合二甲双胍对EGFR-TKIs原发性耐药非小细胞肺癌H1975细胞的抑制作用及其机制研究[J]. 第三军医大学学报, 2017,39(7):668-674.

Yonghong Pan, Lin Jiao, Caiyu Lin, et al. Inhibitory effect and mechanism of gefitinib combined with metformin on EGFR-TKI intrinsic resistant NSCLC H1975 cells[J]. Journal of Third Military Medical University, 2017, 39(7): 668-674.
潘永红, 焦琳, 林采余, 等. 吉非替尼联合二甲双胍对EGFR-TKIs原发性耐药非小细胞肺癌H1975细胞的抑制作用及其机制研究[J]. 第三军医大学学报, 2017,39(7):668-674. DOI： 10.16016/j.1000-5404.201610137.

Yonghong Pan, Lin Jiao, Caiyu Lin, et al. Inhibitory effect and mechanism of gefitinib combined with metformin on EGFR-TKI intrinsic resistant NSCLC H1975 cells[J]. Journal of Third Military Medical University, 2017, 39(7): 668-674. DOI： 10.16016/j.1000-5404.201610137.

摘要

Abstract

Objective

To investigate the synergistic inhibitory effect of gefitinib combined with metformin on non-small cell lung cancer cell line H1975 with intrinsic resistance to EGFR-tyrosine kinase inhibitors (TKIs)

and explore the underlying mechanism.

Methods

After H1975 cells were treated by gefitinib or/and metformin

MTT assay and colony formation assay were used to observe the proliferation of the cells. Cell invasion was tested by matrigel-coated Transwell chamber assay

and migration ability was measured by wound healing assay. TUNEL assay was employed to observe apoptotic rate. The protein levels of apoptosis and epithelial to mesenchymal transition (EMT) related proteins were assayed by immunofluorescence assay and Western blotting.

Results

Gefitinib combined with metformin showed more obviously synergistic inhibitory effect on the proliferation

invasion and migration in H1975 cells than gefitinib alone (

0.05). As compared to the untreated control cells

gefitinib and metformin alone promoted the cell apoptosis. Their combination induced an even higher apoptotic rate in H1975 cells (

0.05)

down-regulated anti-apoptotic proteins Bcl-xl and Mcl-1

up-regulated pro-apoptotic protein Bax

enhanced the EMT reversion

decreased the expression levels of mesenchymal markers

Vimentin

N-cadherin

Slug

Snail while increased the epithelial marker E-cadherin.

Conclusion

Combination of gefitinib and metformin remarkably inhibits the growth

invasion and migration and induces the apoptosis in inherent EGFR-TKIs resistant H1975 cells. The potential mechanism for antitumor might be due to their activation on mitochondrial apoptosis pathway and EMT reversal.

关键词

Keywords

references

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