Author:
Cuan Xiangdan,Yang Xingying,Zhu Weiwei,Zhao Yue,Luo Rui,Huang Yanping,Wang Xuanjun,Sheng Jun
Abstract
Abstract
Background
First-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, have been shown to target tumors with L858R (exon 21) and exon 19 deletions, resulting in significant clinical benefits. However, acquired resistance often occurs due to EGFR mutations. Therefore, novel therapeutic strategies for treatment of patients with EGFR-positive tumors are needed. Berberine (BBR) is an active alkaloid extracted from pharmaceutical plants such as Coptis chinensis. Berberine has been shown to significantly inhibit EGFR activity and mediate anticancer effects in multiple preclinical studies. We investigated whether combining BBR with erlotinib could augment erlotinib-induced cell growth inhibition of EGFR-positive cells in a mouse xenograft model.
Methods
We examined the antitumor activities and potential mechanisms of erlotinib in combination with berberine in vitro and in vivo using the MTT assay, immunoblotting, flow cytometry, and tumor xenograft models.
Results
In vitro studies with A431 cells showed that synergistic cell growth inhibition by the combination of BBR and erlotinib was associated with significantly greater inhibition of pEGFR and pAKT, and inhibition of cyclin D and Bcl-2 expression compared to that observed in response to BBR or erlotinib alone. The efficacy of the combination treatment was also investigated in nude mice. Consistent with the in vitro results, BBR plus erlotinib significantly reduced tumor growth.
Conclusion
Our data supported use of BBR in combination with erlotinib as a novel strategy for treatment of patients with EGFR positive tumors.
Funder
the Yunnan Fundamental Research Project
the Research Start-up Fund of Yunnan Agricultural University
the Science and Technology Plan Project of Yunnan Province
the Yunnan Provincial Key Programs of Yunnan Eco-friendly Food International Cooperation Research Center Project
the Major Scientific and Technological Special Project of Yunnan Province
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Pharmacology
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献