title: The role of IGFBP-5 in mediating the anti-proliferation effect of tetrandrine in human colon cancer cells.
abstract: Colon cancer is one of the most common malignancies, causes considerable morbidity and mortality. The current treatment for colon cancer is more modest than had been hoped. There is an urgent clinical need to explore new agents or adjuvants for colon cancer treatment. Natural products and their derivates act as one of the major source for anticancer agent. In the present study, we investigated the anti-proliferation and chemoprevention effects of tetrandrine (Tet) on colon cancer cells to uncover the possible molecular basis of this effect. We found that Tet can inhibit proliferation and induce apoptosis in LoVo cells. With dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) induced colon cancer model, we found that Tet can prevent or inhibit DMH plus DSS induced aberrant crypt foci (ACF) and colon cancer formation, as well as suppress tumor growth in the xenograft colon cancer model. Tet can downregulate the expression of IGFBP-5 in LoVo cells. Exogenous expression of IGFBP-5 can attenuate the anti-cancer activity of Tet, while IGFBP-5 knockdown potentiates this effect of Tet on LoVo cells. Tet can inhibit Wnt/β-catenin signaling transduction, which can be partly reversed by exogenous expression of IGFBP-5, but is enhanced by IGFBP-5 knockdown. Our results demonstrated that the anticancer activity of Tet in colon cancer cells may be mediated partly by downregulating the expression of IGFBP-5, thus inactivating Wnt/β-catenin signaling transduction.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Mi
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qiu-Xiang
authors.initials: QX
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Shuang-Xu
authors.initials: SX
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jie-Li
authors.initials: JL
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jun-Qin
authors.initials: JQ
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Sun
authors.affiliation: Department of Forensic Medicine, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Wan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Bai-Cheng
authors.initials: BC
authors.lastname: He
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D018975:Insulin-Like Growth Factor Binding Protein 5; D034741:RNA, Small Interfering; C009438:tetrandrine