title: 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.
abstract: 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.
authors.affiliation: Department of Clinical Oncology, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Department of Clinical Oncology, Ping Ding Shan First People's Hospital, Henan 467000, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Kang
authors.forename: Zhen-Ye
authors.initials: ZY
authors.lastname: Xu
authors.forename: Ya-Bin
authors.initials: YB
authors.lastname: Gong
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Wang
authors.forename: Zhong-Qi
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Cao
authors.forename: Ming-Juan
authors.initials: MJ
authors.lastname: Liao