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.
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.
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK jiangw@cf.ac.uk.
Wen G
WG
Jiang
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK.
Lin
L
Ye
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK.
Fiona
F
Ruge
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK.
Ping-Hui
PH
Sun
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK.
Andrew J
AJ
Sanders
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK.
Ki
K
Ji
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK.
Jane
J
Lane
Department of Thoracic Surgery, Peking University Cancer Hospital, Haidian, Beijing, P.R. China.
Lijian
L
Zhang
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK.
Lucy
L
Satherley
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK.
Hoi P
HP
Weeks
Cancer Institute of Capital Medical University and Department of Thoracic Surgery, XuanWu Hospital, Capital Medical University, Beijing, P.R. China.
Xiuyi
X
Zhi
Yiling Medical Research Institute, Shijiazhuang, Hebei Province, P.R. China.
Yong
Y
Gao
Yiling Medical Research Institute, Shijiazhuang, Hebei Province, P.R. China.
Cong
C
Wei
Yiling Medical Research Institute, Shijiazhuang, Hebei Province, P.R. China.
Yiling
Y
Wu
Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Cardiff, UK.
Malcolm D
MD
Mason
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D014704:Veratrum Alkaloids / Q000494:pharmacology
D004365:Drugs, Chinese Herbal; D053823:Hedgehog Proteins; C509239:SHH protein, human; D014704:Veratrum Alkaloids; C579032:yangzheng xiaoji; C000541:cyclopamine
Gli; Smo; Sonic hedgehog (SHH); YangZheng XiaoJi; cellular migration; cyclopamine; invasion; lung cancer; tumor model