title: Periostin induces chemoresistance in colon cancer cells through activation of the PI3K/Akt/survivin pathway.
abstract: In the present study, we aimed to explore the effects of periostin, a cell adhesion protein, on chemoresistance in colon cancer cells. Reverse-transcription polymerase chain reaction and Western blot analyses were employed to detect periostin expression in SW480 and HT-29 colon cancer cells treated with oxaliplatin or fluorouracil (5-FU). Small interfering RNA was used to downregulate endogenous periostin. Annexin-V/propidium iodide staining was performed to analyze the effects of periostin on drug-induced apoptosis. The results showed that treatment with oxaliplatin or 5-FU elevated both the mRNA and protein levels of periostin in SW480 and HT-29 cells. Silencing of periostin significantly (P < 0.01) augmented drug-induced apoptosis in colon cancer cells, coupled with enhanced cleavage of caspase-3 and poly(ADP-ribose) polymerase. Mechanistic studies revealed that periostin silencing significantly (P < 0.01) suppressed the expression of survivin, an antiapoptotic protein in colon cancer cells. Enforced expression of survivin repressed drug-induced apoptosis in periostin-depleted SW480 and HT-29 cells. Additionally, periostin overexpression increased the expression of survivin and the phosphorylation of Akt, which was reversed by pretreatment with the phosphatidylinositol 3-kinase (PI3K)-specific inhibitor LY294002. Taken together, our data demonstrate that periostin induces chemoresistance in colon cancer cells through activation of the PI3K/Akt/survivin pathway.
authors.affiliation: Department of Gastroenterology, The Third Hospital of Xiangya, Central South University, Changsha, People's Republic of China.
authors.forename: Zhi-ming
authors.initials: ZM
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology, The Third Hospital of Xiangya, Central South University, Changsha, People's Republic of China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Emergency, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
authors.forename: Ai-min
authors.initials: AM
authors.lastname: Wang
mesh_terms: D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D015815:Cell Adhesion Molecules; D009944:Organoplatinum Compounds; C512835:POSTN protein, human; D000077150:Oxaliplatin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil
keywords: apoptosis; chemotherapy; drug resistance; periostin; signaling pathway