title: Hedgehog-glioma-associated oncogene homolog-1 signaling in colon cancer cells and its role in the celecoxib-mediated anti-cancer effect.
abstract: Hedgehog (Hh) signaling is activated in numerous malignant tumors, but its role in human colorectal cancer remains uncertain. Celecoxib, a selective cyclooxygenase-2 inhibitor, has been shown to exhibit chemoprevention in colorectal cancer, however, the effects of celecoxib on Hh signaling remain unknown. The current study presents an evaluation of Hh signaling in colon cancer cell lines and the effects of celecoxibin vitro. Active Hh signaling was observed in LoVo and HT-29 cells, with particularly high levels in the LoVo cells. However, Hh signaling activity was absent in HCT-116 cells. Quantitative polymerase chain reaction indicated that the expression of Hh receptor patched homolog 1 (PTCH1) was absent in the LoVo cells, but that they exhibited high levels of glioma-associated oncogene homolog-1 (GLI1) expression, while high expression levels ofPTCH1and low expression levels of smoothened (SMO) andGLI1were observed in the HCT-116 cells. The HCT-116 cells were extremely sensitive to celecoxib, whereas the LoVo cells were resistant to the anticancer effect of the drug. Celecoxib downregulated the expression ofGLI1in the HCT-116 and HT-29 cells, but did not change the expression ofGLI1in the LoVo cells. The results presented in this study indicated that the anticancer effect of celecoxib is selective in colon cancer cells; celecoxib may target cancer cells via the SMO-independent modulation of GLI1 activity, and Hh signaling may be significant in maintaining the malignant state of LoVo cells. These findings may aid in improving our understanding of the carcinogenesis of colon cancer and the development of novel approaches for the targeted therapy of this disease.
authors.affiliation: Department of Pathology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ke
authors.affiliation: Department of Pathology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
keywords: celecoxib; colon cancer cells; cyclopamine; glioma-associated oncogene homolog-1; hedgehog signaling