Marsdenia tenacissima extract enhances gefitinib efficacy in non-small cell lung cancer xenografts
Marsdenia tenacissima extract enhances gefitinib efficacy in non-small cell lung cancer xenografts
复制标题
Marsdenia tenacissima 提取物增强吉非替尼在非小细胞肺癌异种移植物中的疗效
DOI：
10.1016/j.phymed.2015.03.001
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发表时间：
2015-05-15
期刊：
影响因子：
7.9
通讯作者：
Li, Ping-Ping
中科院分区：
文献类型：
--
作者：
Han, Shu-Yan;Zhao, Wei;Li, Ping-Ping
Purpose: The stern of Morsdenia tenacissima (Roxb.) Wight et Arn. has long been used as a medicine to treat cancer in China. Our previous in vitro results showed that Morsdenia tenacissima extract (MTE) overcomes gefitinib resistance in non-small cell lung cancer (NSCLC) cells. However, it is unknown whether MTE could enhance gefitinib efficacy in vivo. The present study was intended to investigate the in vivo anti-tumour activity of MTE combined with gefitinib.Methods: Human NSCLC H460 (K-ras mutation) or H1975 cells (EGER T790M mutation) were subcutaneously inoculated into nude mice. Tumour volume and body weight were measured regularly. Resected tumours were weighed after the animals were sacrificed. Immunoblotting or immunohistochemistry was used to assess the cellular proliferation and apoptosis in xenograft tumour tissue. Expression of the EGER downstream pathways and c-Met were measured with western blot analysis to explore possible mechanisms.Results: MTE (5, 10, 20 g/kg) dose-dependently reduced tumour growth and induced cell apoptosis. MTE suppressed EGER related signals, and 20 g/kg was the most effective dose. Low-dose MTE (5 g/kg) significantly enhanced gefitinib efficacy in resistant H460 and H1975 xenografts. The combination inhibited tumour proliferation and induced cell apoptosis in both resistant NSCLC xenografts. Constitutive activation of the PI3K/Akt and MEK/ERK pathways is related to EGFR-TKI resistance. Accordingly, phosphorylation of PI3K/Akt/mTOR and ERK1/2 was suppressed after combination treatment. Simultaneously, cross-talked c-Met and EGER were also prominently lowered in the presence of MTE combined with gefitinib.Conclusion: The present results suggest that the combination of MTE and gefitinib may be a promising therapeutic approach to enhance gefitinib efficacy in resistant NSCLC. (C) 2015 Elsevier GmbH. All rights reserved.
