SU11274 reverse gefitinib resistance induced by hepatocyte growth factor in different EGFR gene type of non-small cell lung cancer cells

严春花; 玄香兰; 张佳

doi:10.3969/j.issn.1007-3969.2015.02.004

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SU11274 reverse gefitinib resistance induced by hepatocyte growth factor in different EGFR gene type of non-small cell lung cancer cells

更新时间：2025-12-31

- SU11274 reverse gefitinib resistance induced by hepatocyte growth factor in different EGFR gene type of non-small cell lung cancer cells
- China Oncology Vol. 25, Issue 2, Pages: 99-104(2015)
- 作者机构：
  
  1. 延边大学附属医院呼吸内科，延吉,吉林,133000
  2. 延边第二人民医院呼吸内科，延吉,吉林,133000
- 作者简介：
- 基金信息：
- DOI：10.3969/j.issn.1007-3969.2015.02.004
  CLC：
- Published Online：13 May 2015，
  
  Published：13 May 2015
- 稿件说明：
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严春花,玄香兰,张佳,等. SU11274逆转肝细胞生长因子诱导不同EGFR基因型非小细胞肺癌细胞株对吉非替尼耐药[J]. 中国癌症杂志, 2015, 25(2): 99-104.

严春花, 玄香兰, 张佳. SU11274 reverse gefitinib resistance induced by hepatocyte growth factor in different EGFR gene type of non-small cell lung cancer cells[J]. China Oncology, 2015, 25(2): 99-104.
严春花,玄香兰,张佳,等. SU11274逆转肝细胞生长因子诱导不同EGFR基因型非小细胞肺癌细胞株对吉非替尼耐药[J]. 中国癌症杂志, 2015, 25(2): 99-104. DOI： 10.3969/j.issn.1007-3969.2015.02.004.

严春花, 玄香兰, 张佳. SU11274 reverse gefitinib resistance induced by hepatocyte growth factor in different EGFR gene type of non-small cell lung cancer cells[J]. China Oncology, 2015, 25(2): 99-104. DOI： 10.3969/j.issn.1007-3969.2015.02.004.

摘要

背景与目的：肝细胞生长因子(hepatocyte growth factor，HGF)诱导敏感非小细胞肺癌(nonsmall cell lung cancer，NSCLC)细胞对表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor，EGFR-TKI)耐药，其机制与c-Met激活有关。本研究探讨c-Met抑制剂SU11274逆转HGF诱导的不同EGFR基因型NSCLC细胞株对吉非替尼耐药及逆转耐药机制。方法：选择人NSCLC细胞株PC9(EGFR突变型)、H292(EGFR野生型)和A549(EGFR野生型)，应用吉非替尼和SU11274单独或联合作用于HGF诱导的细胞株。实验分为6组：C组(不加药对照组)、H组(HGF处理组)、G组(吉非替尼处理组)、S(SU11274处理组)、HG组(HGF+吉非替尼处理组)和HGS组(HGF+吉非替尼+SU11274处理组)。MTT法检测对细胞增殖的影响，流式细胞术检测细胞凋亡的影响；应用蛋白质印迹法(Western blot)检测细胞中c-Met及其下游通道Stat3、Akt和Erk1/2蛋白表达水平。结果：吉非替尼对3种细胞的生长抑制作用均呈浓度依赖性，HGF处理能够缓解吉非替尼的增殖抑制作用(P0.05)；不同浓度吉非替尼联合SU11274作用于HGF诱导细胞时，3种细胞株存活率比吉非替尼单独作用于HGF诱导细胞时明显降低(P0.05)；HGS组的细胞凋亡比HG组明显增加(P0.05)；HGS组的c-Met、Stat3、Akt和Erk1/2活化蛋白量比HG组明显减少。结论：c-Met抑制剂SU11274可逆转HGF诱导的不同EGFR基因型NSCLC细胞株对吉非替尼耐药，其机制可能与抑制HGF活化的c-Met及其下游通道蛋白表达有关。

Abstract

Background and purpose: Hepatocyte growth factor (HGF) induce epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance in non-small cell lung cancer (NSCLC) cells

the mechanism might be related with activation of c-Met. The present study aimed to explore whether c-Met inhibitor SU11274 reverse gefitinib resistance induced by HGF in different EGFR gene types of NSCLC. Methods: PC9 (EGFR-activating mutant)

H292 (EGFR-wild type) and A549 (EGFR-wiled) were chosen. The experiments were divided into 6 groups: C group (control)

H group (HGF)

G group (gefitinib)

S group (SU11274)

GH group (gefitinib+HGF)

GSH group (gefitinib+SU11274+HGF). The cell survival was measured by MTT assay; the cell apoptosis was measured by flow cytometry (FCM); the expressions of c-Met

Stat3

Akt and Erk1/2 protein were examined by Western blot. Results: Gefitinib inhibited cell growth of 3 cells lines in a dose-dependent manner

and treating with HGF could relieve inhibition of cell growth caused by gefitinib. The cell survival when treating the HGF-induced cell lines with defferent concentration of gefitinib combined with SU11274 was significantly decreased than that when treating HGF-induced cell lines with gefitinib alone. In 3 cell lines

the apoptosis rate in HGS group was higher than that in HG group (P0.05). In three cells lines

the p-Met

p-Stat3

p-Akt and p-Erk1/2 expressions in HGS group were lower than that in HG group (P0.05). Conclusion: SU11274 reversed gefitinib resistance induced by HGF in different EGFR gene types of NSCLC cells

the mechanism might be related with inhibiting the HGF-induced activation of c-Met and its downstream signaling pathway.

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