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Research ArticleExperimental Studies

Expression of Sonic Hedgehog (SHH) in Human Lung Cancer and the Impact of YangZheng XiaoJi on SHH-mediated Biological Function of Lung Cancer Cells and Tumor Growth

WEN G. JIANG, LIN YE, FIONA RUGE, PING-HUI SUN, ANDREW J. SANDERS, KI JI, JANE LANE, LIJIAN ZHANG, LUCY SATHERLEY, HOI P. WEEKS, XIUYI ZHI, YONG GAO, CONG WEI, YILING WU and MALCOLM D. MASON
Anticancer Research March 2015, 35 (3) 1321-1331;
WEN G. JIANG
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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  • For correspondence: jiangw@cf.ac.uk
LIN YE
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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FIONA RUGE
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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PING-HUI SUN
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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ANDREW J. SANDERS
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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KI JI
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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JANE LANE
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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LIJIAN ZHANG
2Department of Thoracic Surgery, Peking University Cancer Hospital, Haidian, Beijing, P.R. China
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LUCY SATHERLEY
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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HOI P. WEEKS
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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XIUYI ZHI
3Cancer Institute of Capital Medical University and Department of Thoracic Surgery, XuanWu Hospital, Capital Medical University, Beijing, P.R. China
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YONG GAO
4Yiling Medical Research Institute, Shijiazhuang, Hebei Province, P.R. China
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CONG WEI
4Yiling Medical Research Institute, Shijiazhuang, Hebei Province, P.R. China
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YILING WU
4Yiling Medical Research Institute, Shijiazhuang, Hebei Province, P.R. China
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MALCOLM D. MASON
1Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK
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Abstract

Sonic Hedgehog (SHH) is a protein that is aberrantly expressed in various human tumors. SHH and its signaling molecules have been indicated as potential therapeutic targets. In the present study, we evaluated the expression of SHH transcript in human non-small cell lung cancer (NSCLC) tissues and investigated the impact of inhibiting SHH together with a traditional Chinese medicine formula, YangZheng XiaoJi (YZXJ), on the function and growth of lung cancer cells. Human NSCLC tissues had significantly higher levels of the SHH transcript compared matched normal lung tissues (n=83). TNM2 tumors and tumors with pleural invasion had higher levels than TNM1 and non-invasive tumors. High SHH levels were associated with a shorter overall survival (OS) of the patients. A SHH inhibitor, cyclopamine, and YZXJ alone or in combination had a marked inhibitory effect on cellular invasion and cellular migration of human lung cancer cells, A549 and SKMES1. YangZheng XiaoJi and its combination with cyclopamine also significantly reduced the growth of lung tumors in vivo together with a reduction of SHH and smoothened (Smo) proteins in the lung tumors. The present study provides evidence that blocking SHH by way of small inhibitor and by YangZheng XiaoJi has a profound influence on lung cancer cells as seen by in vitro invasion and cell migration and in vivo tumor growth. Together with the aberrant expression of SHH in NSCLC tumors in the patients, it is suggested that SHH is a potential target for therapies for NSCLC.

  • Sonic hedgehog (SHH)
  • lung cancer
  • tumor model
  • YangZheng XiaoJi
  • cellular migration
  • invasion
  • cyclopamine
  • Smo
  • Gli
  • Received November 16, 2014.
  • Revision received November 25, 2014.
  • Accepted December 2, 2014.
  • Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 35 (3)
Anticancer Research
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March 2015
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Expression of Sonic Hedgehog (SHH) in Human Lung Cancer and the Impact of YangZheng XiaoJi on SHH-mediated Biological Function of Lung Cancer Cells and Tumor Growth
WEN G. JIANG, LIN YE, FIONA RUGE, PING-HUI SUN, ANDREW J. SANDERS, KI JI, JANE LANE, LIJIAN ZHANG, LUCY SATHERLEY, HOI P. WEEKS, XIUYI ZHI, YONG GAO, CONG WEI, YILING WU, MALCOLM D. MASON
Anticancer Research Mar 2015, 35 (3) 1321-1331;

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Expression of Sonic Hedgehog (SHH) in Human Lung Cancer and the Impact of YangZheng XiaoJi on SHH-mediated Biological Function of Lung Cancer Cells and Tumor Growth
WEN G. JIANG, LIN YE, FIONA RUGE, PING-HUI SUN, ANDREW J. SANDERS, KI JI, JANE LANE, LIJIAN ZHANG, LUCY SATHERLEY, HOI P. WEEKS, XIUYI ZHI, YONG GAO, CONG WEI, YILING WU, MALCOLM D. MASON
Anticancer Research Mar 2015, 35 (3) 1321-1331;
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Keywords

  • Sonic hedgehog (SHH)
  • lung cancer
  • tumor model
  • YangZheng XiaoJi
  • cellular migration
  • invasion
  • cyclopamine
  • Smo
  • Gli
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