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Cancer Med. 2018 Jan;7(1):208-218. doi: 10.1002/cam4.1269. Epub 2017 Dec 13.

Oxymatrine inhibits non-small cell lung cancer via suppression of EGFR signaling pathway.

Li W1,2,3,4, Yu X5, Tan S6, Liu W7, Zhou L8, Liu H1,2.

Author information

1
Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
2
Clinical Center for Gene Diagnosis and Therapy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
3
Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
4
Cell Transplantation and Gene Therapy Institute, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
5
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, 44195, USA.
6
Department of Hemopathology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China.
7
Department of Pathology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China.
8
Department of Pathology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.

Abstract

Epidermal growth factor receptor (EGFR) plays a crucial role in human non-small cell lung cancer (NSCLC) tumorigenesis. In this study, oxymatrine was identified as an EGFR signaling pathway inhibitor in NSCLC. Oxymatrine inhibited anchorage-dependent and independent growth of NSCLC cell lines but had no cytotoxicity in normal lung cells. We found that exposure to oxymatrine not only suppressed the activity of wild-type EGFR but also inhibited the activation of exon 19 deletion and L858R/T790M mutated EGFR. Flow cytometry analysis suggested that oxymatrine-induced cell cycle G0/G1 arrest was dependent on EGFR-Akt signaling. Exogenous overexpression of Myr-Akt rescued cyclin D1 expression in HCC827 cells. Moreover, oxymatrine prominently suppressed tumor growth in a xenograft mouse model. Thus, oxymatrine appears to be a novel therapeutic agent for NSCLC treatment.

KEYWORDS:

Akt; cyclin D1; epidermal growth factor receptor; non-small cell lung cancer; oxymatrine

PMID:
29239135
PMCID:
PMC5773973
DOI:
10.1002/cam4.1269
[Indexed for MEDLINE]
Free PMC Article

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