Cucurbitacin E inhibits the Yes-associated protein signaling pathway and suppresses brain metastasis of human non-small cell lung cancer in a murine model
机构：[1]Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco,San Francisco, CA 94115, USA[2]Department of Thoracic Medicine, Chang Gung Memorial Hospital Linkou Branch,Taoyuan 33305[3]School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, R.O.C.[4]Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine,University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, P.R. China外科中心胸外科中心四川省肿瘤医院胸外科[5]Department of Pathology, University of California, San Francisco, San Francisco, CA 94115, USA
Human non-small cell lung cancer (NSCLC) is associated with an extremely poor prognosis especially for the 40% of patients who develop brain metastasis, and few treatment strategies exist. Cucurbitacin E (CuE), an oxygenated tetracyclic triterpenoid isolated from plants particularly of the family Cucurbitaceae, has shown anti-tumorigenic properties in several types of cancer, yet the mechanism remains unclear. Yes-associated protein (YAP), a main mediator of the Hippo signaling pathway, promotes tumorigenesis, drug resistance and metastasis in human NSCLC. The present study was designed to ascertain whether CuE inhibits YAP and its downstream gene expression in the human NSCLC cell lines H2030-BrM3 (K-ras(G12C) mutation) and PC9-BrM3 (EGFR(Delta exon19) mutation), which have high potential for brain metastasis. The efficacy of CuE in suppressing brain metastasis of H2030-BrM3 cells in a murine model was also investigated. It was found that after CuE treatment in H2030-BrM3 and PC9-BrM3 cells, YAP protein expression was decreased, and YAP signaling GTIIC reporter activity and expression of the downstream genes CTGF and CYR61 were significantly (P<0.01) decreased. CuE treatment also reduced the migration and invasion abilities of the H2030-BrM3 and PC9-BrM3 cells. Finally, our in vivo study showed that CuE treatment (0.2 mg/kg) suppressed H2030-BrM3 cell brain metastasis and that mice treated with CuE survived longer than the control mice treated with 10% DMSO (P=0.02). The present study is the first to demonstrate that CuE treatment inhibits YAP and the signaling downstream gene expression in human NSCLC in vitro, and suppresses brain metastasis of NSCLC in a murine model. More studies to verify the promising efficacy of CuE in inhibiting brain metastasis of NSCLC and various other cancers may be warranted.
基金：
National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 CA140654]; Chang-Gung Medical Research Project (CMRP) [CMRPG3G1661, CMRPG5H0141]; Kazan McClain Partner's Foundation; Estate of Robert Griffiths; Estate of Norman Mancini; Barbara Isackson Lung Cancer Research Fund; Jeffrey and Karen Peterson Family Foundation
第一作者机构：[1]Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco,San Francisco, CA 94115, USA[2]Department of Thoracic Medicine, Chang Gung Memorial Hospital Linkou Branch,Taoyuan 33305[3]School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, R.O.C.
通讯作者：
通讯机构：[1]Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco,San Francisco, CA 94115, USA[*1]Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 2340 Sutter Street, N‑221, San Francisco, CA 94115, USA
推荐引用方式(GB/T 7714)：
Hsu Ping-Chih,Tian Bo,Yang Yi-Lin,et al.Cucurbitacin E inhibits the Yes-associated protein signaling pathway and suppresses brain metastasis of human non-small cell lung cancer in a murine model[J].ONCOLOGY REPORTS.2019,42(2):697-707.doi:10.3892/or.2019.7207.
APA：
Hsu, Ping-Chih,Tian, Bo,Yang, Yi-Lin,Wang, Yu-Cheng,Liu, Shu...&You, Liang.(2019).Cucurbitacin E inhibits the Yes-associated protein signaling pathway and suppresses brain metastasis of human non-small cell lung cancer in a murine model.ONCOLOGY REPORTS,42,(2)
MLA：
Hsu, Ping-Chih,et al."Cucurbitacin E inhibits the Yes-associated protein signaling pathway and suppresses brain metastasis of human non-small cell lung cancer in a murine model".ONCOLOGY REPORTS 42..2(2019):697-707
