Chinese Herbal Medicine Wenxia Changfu Formula Reverses Cell Adhesion-Mediated Drug Resistance via the Integrin β1-PI3K-AKT Pathway in Lung Cancer
Authors: ZhiChun Wu
HuaXin Wang
YaNan Zhang
ShiJun Wang
Guowei Liu
XuMing Ji
HuaYun Yu
Journal: Journal of Cancer (2019)
Discipline: CLINICAL MEDICINE
Keywords: combination therapy; integrin β1; lung cancer; traditional Chinese medicine.
Affiliations: College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shangdong Province 250355, China., Shandong Provincial Chinese Medicine Classical Prescription Demonstration Engineering Technology Research Center, Jinan, Shangdong Province 250355, China., College of Basic Medicine,Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province 310053, China.

Abstract:  In the treatment of lung cancer, the multidrug resistance to chemotherapeutic drugs is one of the reasons of low rates for cure and treatment failure, the combination of chemotherapeutic drugs and traditional Chinese medicine can increase the sensitivity of chemotherapy and reduce its adverse effects. Our previous study has proved that Chinese herbal medicine (CHM) Wenxia Changfu Formula (WCF for short) effectively enhances chemotherapeutic efficacy in lung cancer treatment and reverses multidrug resistance in lung cancer cells in vitro. The present study aims to investigate the effect and mechanism of WCF in reversing cell adhesion-mediated drug resistance of lung cancer by using A549 three-dimensional cell culture and nude mouse model of the A549 cell line with Integrin β1 overexpression. We show that the combination of WCF with DDP can decrease proliferation of lung cancer cells by inducing cell cycle arrest and apoptosis. Moreover, we find that the combination of WCF with DDP suppresses the expression of certain molecules which regulate cell cycle and apoptosis. Mechanistically, we show that the Integrin β1, FAK, PI3K, and AKT protein expressions are suppressed by DDP and even more responses are observed when DDP and WCF are combined, showing WCF treatment enhances the effect of commonly used anticancer drugs. In line with the above findings, our results confirm that WCF reverses cell adhesion-mediated drug resistance of lung cancer via inactivating Integrin β1/PI3K/AKT and apoptosis induction. 

Retracted: No

PubPeer comments:
 An image in Figure 7 shares unexpected similarities with an image in Figure 6F of a different paper: Frontiers in Pharmacology (2018), doi: 10.3389 fphar.2018.00881, discussed here: https: pubpeer.com publications 66F4461C8873CA046F683A7215C2A1 There does not appear to be any overlap between the authors or affiliations. Given the dates that the papers were received and were published, I am not entirely certain which group had the image first... perhaps a third party was involved? *** ![file] *** Acknowledgments Supported by the National Natural Science Foundation of China (No.81774198, 81703839, 815738 71, 81273634), and Key Technological Innovation Project of Key Industries in Shandong Province (No.2016CYJS08A01-3, 2016CYJS08A01-4, 2016ZDJS0 7A12). The Natural Science Foundation of Shandong Province (No.ZR2014HQ032) and Shandong Province Administration of TCM also supported the work (NO.2015-016, 2017-009). ,