肝细胞生长因子诱导非小细胞肺癌耐药研究
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摘要
目的探讨肝细胞生长因子诱导敏感非小细胞肺癌细胞对吉非替尼的耐药性及其机制。方法应用肝细胞生长因子分别诱导两种不同基因类型非小细胞肺癌细胞,依次开展细胞增殖、凋亡及细胞周期等检验,分析其对吉非替尼的耐药性及机制。结果 PC-9与H292细胞对吉非替尼的生长抑制效果与药物浓度呈负相关性,经肝细胞生长因子诱导后其半数抑制浓度明显上升。肝细胞生长因子在两种细胞对吉非替尼耐药方面有诱导作用,对PC-9细胞凋亡有明显影响,但对两种细胞周期均无显著影响,并且对两种肺癌细胞c-MET磷酸化均有刺激作用。结论肝细胞生长因子可诱导非小细胞肺癌细胞对吉非替尼耐药,其作用机制或为刺激细胞c-MET磷酸化表达增强
Objective To investigate the resistance of hepatocyte growth factor(HGF) induced sensitive non-small cell lung cancer(NSCLC) cells to gefitinib and its mechanism. Methods Hepatocyte growth factor(HGF) was used to induce two different gene types of nonsmall cell lung cancer(NSCLC) cells. Cell proliferation, apoptosis and cell cycle tests were carried out in turn to analyze the resistance to gefitinib and its mechanism. Results The inhibitory effect of PC-9 and H292 cells on the growth of gefitinib was negatively correlated with the drug concentration, and half of the inhibitory concentration increased significantly after induction by hepatocyte growth factor. Hepatocyte growth factor(HGF) could induce gefitinib resistance in both kinds of cells, and had a significant effect on apoptosis of PC-9 cells, but had no significant effect on both cell cycles, and can stimulate c-MET phosphorylation in both kinds of lung cancer cells. Conclusion Hepatocyte growth factor can induce gefitinib resistance in non-small cell lung cancer cells by stimulating c-MET phosphorylation.
Objective To investigate the resistance of hepatocyte growth factor(HGF) induced sensitive non-small cell lung cancer(NSCLC) cells to gefitinib and its mechanism. Methods Hepatocyte growth factor(HGF) was used to induce two different gene types of nonsmall cell lung cancer(NSCLC) cells. Cell proliferation, apoptosis and cell cycle tests were carried out in turn to analyze the resistance to gefitinib and its mechanism. Results The inhibitory effect of PC-9 and H292 cells on the growth of gefitinib was negatively correlated with the drug concentration, and half of the inhibitory concentration increased significantly after induction by hepatocyte growth factor. Hepatocyte growth factor(HGF) could induce gefitinib resistance in both kinds of cells, and had a significant effect on apoptosis of PC-9 cells, but had no significant effect on both cell cycles, and can stimulate c-MET phosphorylation in both kinds of lung cancer cells. Conclusion Hepatocyte growth factor can induce gefitinib resistance in non-small cell lung cancer cells by stimulating c-MET phosphorylation.
引文
[1]严春花,吴叶丹,安昌善.SU11274逆转肝细胞生长因子诱导的非小细胞肺癌细胞对厄洛替尼耐药作用及其机制研究[J].中国全科医学,2017,20(14):1707-1711.
[2]潘永红,焦琳,林采余,等.吉非替尼联合二甲双胍对EGFRTKIs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.
[3]吴美玉,玄香兰,王富佳,等.c-Met抑制剂SU11274在HGF诱导不同EGFR基因型非小细胞肺癌细胞对厄罗替尼耐药的逆转作用[J].中国肿瘤生物治疗杂志,2015,32(4):427-431.
[4]崔青松,朴红梅,崔晶刚,等.肝细胞生长因子诱导敏感非小细胞肺癌细胞对厄洛替尼耐药及机制研究[J].中国全科医学,2017,20(9):1076-1083.
[5]蔡雪婷,杨杰,胡春萍,等.双氢青蒿素通过抑制STAT3增加非小细胞肺癌细胞对吉非替尼的敏感性[J].科学通报,2017,62(18):2013-2019.
[6]方利洲,刘凌,张剑青,等.吉非替尼对中、晚期非小细胞肺癌患者血清MMP-7、MMP-9表达的影响[J].基因组学与应用生物学,2016,35(11):2909-2915.
[7]江冠铭,贾筠,陈镜塘,等.化学治疗交替吉非替尼治疗EGFR突变阳性的晚期非小细胞肺癌的疗效和安全性[J].新医学,2015,28(6):391-394.
[8]张火兵,童能胜,苍宏宇,等.分析吉非替尼敏感性与耐药性非小细胞肺癌患者临床特征和血清中相关标志物的水平变化[J].标记免疫分析与临床,2018,25(2):162-166.
[9]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.
[10]陈琦,李雄英,唐夏焘.榄香烯通过c-Met信号通路逆转由肝细胞生长因子诱导的吉非替尼耐药作用[J].中国病理生理杂志,2018,34(3):469-473.
[11]李思文,夏旭,胡宁东,等.肝细胞生长因子对非小细胞肺癌侵袭和迁移的影响[J].广东医学,2017,38(2):173-177.
[12]王秀丽,展翼翼,周欣.非小细胞肺癌患者血清中肝细胞生长因子水平检测与EGFR基因突变的关系[J].中国社区医师,2017,33(28):5-6.
[2]潘永红,焦琳,林采余,等.吉非替尼联合二甲双胍对EGFRTKIs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.
[3]吴美玉,玄香兰,王富佳,等.c-Met抑制剂SU11274在HGF诱导不同EGFR基因型非小细胞肺癌细胞对厄罗替尼耐药的逆转作用[J].中国肿瘤生物治疗杂志,2015,32(4):427-431.
[4]崔青松,朴红梅,崔晶刚,等.肝细胞生长因子诱导敏感非小细胞肺癌细胞对厄洛替尼耐药及机制研究[J].中国全科医学,2017,20(9):1076-1083.
[5]蔡雪婷,杨杰,胡春萍,等.双氢青蒿素通过抑制STAT3增加非小细胞肺癌细胞对吉非替尼的敏感性[J].科学通报,2017,62(18):2013-2019.
[6]方利洲,刘凌,张剑青,等.吉非替尼对中、晚期非小细胞肺癌患者血清MMP-7、MMP-9表达的影响[J].基因组学与应用生物学,2016,35(11):2909-2915.
[7]江冠铭,贾筠,陈镜塘,等.化学治疗交替吉非替尼治疗EGFR突变阳性的晚期非小细胞肺癌的疗效和安全性[J].新医学,2015,28(6):391-394.
[8]张火兵,童能胜,苍宏宇,等.分析吉非替尼敏感性与耐药性非小细胞肺癌患者临床特征和血清中相关标志物的水平变化[J].标记免疫分析与临床,2018,25(2):162-166.
[9]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.
[10]陈琦,李雄英,唐夏焘.榄香烯通过c-Met信号通路逆转由肝细胞生长因子诱导的吉非替尼耐药作用[J].中国病理生理杂志,2018,34(3):469-473.
[11]李思文,夏旭,胡宁东,等.肝细胞生长因子对非小细胞肺癌侵袭和迁移的影响[J].广东医学,2017,38(2):173-177.
[12]王秀丽,展翼翼,周欣.非小细胞肺癌患者血清中肝细胞生长因子水平检测与EGFR基因突变的关系[J].中国社区医师,2017,33(28):5-6.