title: Gap junction composed of connexin43 modulates 5‑fluorouracil, oxaliplatin and irinotecan resistance on colorectal cancers.
abstract: Chemotherapy is one of the most commonly used therapeutic strategies for metastatic colon cancer. However, the development of resistance to chemotherapeutic agents limits their application in clinical use. The underlying mechanisms of this resistance development require further elucidation. The current study investigated the effects of connexin43 (Cx43) gap junctions on 5‑fluorouracil (5‑FU), oxaliplatin and irinotecan in colon cancer cells. Three different methods were used to manipulate Cx43 gap junction function: i) Cell culture at different densities; ii) pretreatment with a Cx43 specific inhibitor or enhancer; and iii) Cx43 gene knock‑down. Results indicated that the cell toxicity of 5‑FU, oxaliplatin and irinotecan was cell density‑dependent, which was mediated by gap junctions. Downregulation of Cx43 gap junction functioning attenuated 5‑FU, oxaliplatin and irinotecan toxicity in colon cancer cells, which was increased in cells treated with a Cx43 gap junction function enhancer. Thus, the results of the present study suggest that resistance to 5‑FU, oxaliplatin and irinotecan in colon cancer cells was relative to Cx43 expression loss as cancer developed, which may indicate a novel basis for therapeutic strategy development to combat drug resistance in numerous cell types, in addition to colon cancer cells.
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Zhao-Wei
authors.initials: ZW
authors.lastname: Zou
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Hai-Jin
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Zong-Hai
authors.initials: ZH
authors.lastname: Huang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Shun
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005472:Fluorouracil / Q000494:pharmacology*; D017629:Gap Junctions / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D000077146:Irinotecan; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D018031:Connexin 43; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin