title: Suppressive effect of sinomenine combined with 5-fluorouracil on colon carcinoma cell growth.
abstract: It is reported that sinomenine (SIN) and 5-fluorouracil (5-FU) both are effective for colon cancer, but their cooperative suppressive effects and toxicity remain to be clarified in detail. This study aimed to determine suppressive effects and toxicity of sinomenine (SIN) plus 5-fluorouracil (5-FU) on LoVo colon carcinoma cells in vitro and in vivo. CCK-8, Hoechst 33258 staining and an annexin V-FITC/PI apoptosis kit were used to detect suppressive effects. Western blotting was applied to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis. SIN or 5-FU or both were injected into nude mice, and then suppressive effects and side effects were observed. SIN plus 5-FU apparently inhibited the proliferation of LoVo cells and induced apoptosis. Moreover the united effects were stronger than individually (p<0.05). The results of annexin V-FITC /PI staining and Hoechst 33258 staining showed that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone was significantly higher than the control group (p<0.05). Expression of Bax and Bcl-2 was up-regulated and down-regulated respectively. SIN or 5-FU significantly inhibited effects on the volume of tumour xenografts and their combined suppressive effects were stronger (p<0.05). No obvious side effects were observed. It was apparent that the united effects of SIN and 5-FU on the growth of colorectal carcinoma LoVo cells in vitro and in vivo were superior to those using them individually, and it did not markedly increase the side effects of chemotherapy.
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, China E-mail : dwg@whu.edu.cn.
authors.forename: Ji-Xiang
authors.initials: JX
authors.lastname: Zhang
authors.forename: Zi-Rong
authors.initials: ZR
authors.lastname: Yang
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wu
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Guo
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Dong
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009019:Morphinans / Q000009:adverse effects / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D000964:Antimetabolites, Antineoplastic; D009019:Morphinans; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C009271:sinomenine; D005472:Fluorouracil