Bufalin Reverses HGF-Induced Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer Cells via Blockage of Met/PI3k/Akt Pathway and Induction of Apoptosis.
Bufalin Reverses HGF-Induced Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer Cells via Blockage of Met/PI3k/Akt Pathway and Induction of Apoptosis.
复制标题
Bufalin通过阻塞/PI3K/AKT途径和诱导凋亡逆转了HGF诱导的EGFR-TKIS对EGFR-TKIS的抗性。
DOI：
10.1155/2013/243859
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Liao MJ
中科院分区：
文献类型：
--
作者：
Kang XH;Xu ZY;Gong YB;Wang LF;Wang ZQ;Xu L;Cao F;Liao MJ
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），如吉非替尼（gefitinib）和厄洛替尼（erlotinib），对表皮生长因子受体（EGFR-）激活突变的非小细胞肺癌（NSCLC）患者显示出良好的治疗效果。然而，获得性耐药导致的不可避免的复发限制了治疗结果的临床改善。许多研究表明肝细胞生长因子-（HGF-）Met轴在肿瘤的进展和药物敏感性中起重要作用。HGF可能通过Met/PI 3 K/Akt信号通路诱导EGFR突变型肺癌细胞对EGFR-TKI的耐药。本研究的目的是确定蟾酥的主要生物活性成分蟾毒灵是否可以逆转突变型肺癌细胞PC-9、HCC 827和H1975对HGF诱导的可逆和不可逆EGFR TKI的抗性。我们的研究表明蟾毒灵可通过抑制Met/PI 3 K/Akt通路，诱导死亡信号，逆转EGFR突变肺癌细胞对外源性HGF诱导的可逆和不可逆EGFR-TKI的耐药。这些结果表明蟾毒灵可能具有克服HGF诱导的肺癌分子靶向药物耐药性的潜力。
The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, have shown promising therapeutic efficacy in nonsmall cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor- (EGFR-) activating mutation. However, the inevitable recurrence resulting from acquired resistance has limited the clinical improvement in therapy outcomes. Many studies demonstrate that hepatocyte growth factor- (HGF-) Met axis plays an important role in tumor progression and drug sensitivity. HGF may induce resistance to EGFR-TKIs in EGFR mutant lung cancer cells by Met/PI3K/Akt signaling. The purpose of this study was to determine whether bufalin, a major bioactive component of Venenum Bufonis, could reverse HGF-induced resistance to reversible and irreversible EGFR-TKIs in mutant lung cancer cells PC-9, HCC827, and H1975. Our studies showed that bufalin could reverse resistance to reversible and irreversible EGFR-TKIs induced by exogenous HGF in EGFR mutant lung cancer cells by inhibiting the Met/PI3K/Akt pathway and inducing death signaling. These results suggested that bufalin might have a potential to overcome HGF-induced resistance to molecular-targeted drugs for lung cancer.
登录
查看更多内容
影响因子：
51.1
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro
影响因子：
4.2
作者：
Li, Huaxing;Wang, Peng;Yang, Peying
通讯作者：
Yang, Peying
DOI：
10.1016/j.jsbmb.2009.01.022
发表时间：
2009-04-01
影响因子：
4.1
作者：
Amano, Yusuke;Cho, Yoshitake;Makishima, Makoto
通讯作者：
Makishima, Makoto
影响因子：
2.2
作者：
GREEN, LM;READE, JL;WARE, CF
通讯作者：
WARE, CF
DOI：
10.1073/pnas.0502860102
发表时间：
2005-05-24
影响因子：
11.1
作者：
Kwak, EL;Sordella, R;Haber, DA
通讯作者：
Haber, DA