Upregulation of periostin prevents P53-mediated apoptosis in SGC-7901 gastric cancer cells.
Periostin is frequently upregulated in human cancers including gastric cancer and implicated in cancer cell proliferation, invasion, and epithelial-mesenchymal transition. This study was undertaken to investigate the effects of periostin overexpression on the chemosensitivity of gastric cancer cells. We constructed a stable cell line overexpressing periostin in SGC-7901 human gastric cancer cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed that periostin had no influence on the proliferation of SGC-7901 cells. Compared to empty vector-transfected cells, overexpression of periostin rendered SGC-7901 cells more resistant to cisplatin or 5-fluorouracil (5-FU)-induced apoptosis, accompanying with less release of cytochrome c from mitochondria and diminished cleavage of caspase-3 and poly (ADP-ribose) polymerase. Periostin-overexpressing cells treated with cisplatin or 5-FU showed significantly (p < 0.05) decreased expression of Bax and p53 proteins and increased expression of Bcl-2 protein, when compared to drug-treated mock counterparts. Restoration of p53 expression by delivering wild-type p53 gene resulted in a marked increase in drug-induced apoptosis in periostin-overexpressing SGC-7901 cells. Periostin overexpression elevated the phosphorylation of Akt. Pretreatment of periostin-overexpressing cells with an Akt inhibitor, MK-2206, partially rescued periostin-mediated inhibition of p53 expression and drug resistance. Taken together, our data indicate that periostin confers protection against cisplatin or 5-FU-induced apoptosis in SGC-7901 cells, likely through modulating the Akt/p53 pathway, and thus represents a potential therapeutic target in gastric cancer.
Department of Gastroenterology, The First Affiliated Hospital, Jilin University, Jilin, 1300112, China.
Bin
B
Li
Liyan
L
Wang
Baorong
B
Chi
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D058990:Molecular Targeted Therapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D015854:Up-Regulation
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin; D005472:Fluorouracil