RRC ID 37840
著者 Oda A, Katayose Y, Yabuuchi S, Yamamoto K, Mizuma M, Shirasou S, Onogawa T, Ohtsuka H, Yoshida H, Hayashi H, Rikiyama T, Kim H, Choe Y, Kim K, Son H, Motoi F, Egawa S, Unno M.
タイトル Clock gene mouse period2 overexpression inhibits growth of human pancreatic cancer cells and has synergistic effect with cisplatin.
ジャーナル Anticancer Res
Abstract Circadian rhythms are the daily oscillations of multiple biological processes regulated by an endogenous clock. The Period2 gene is essential in controlling the circadian rhythm and plays an important role in tumor suppression. We examined whether the overexpression of the mouse Period2 gene (mPer2) in cultured tumor cells from human tissues inhibits cell growth, using the recombinant adenovirus vector AdmPer2. The overexpression of mPer2 in human pancreatic cancer cells (Panc1, Aspc1) reduced cellular proliferation and induced apoptotic cell death. Infection with AdmPer2 also inhibited cell-cycle progression, inducing arrest at the G(2)-M phase. Western blotting analyses confirmed that infection with AdmPer2 reduced Bcl-X(L), Cdc2 and cyclin B1 protein, whereas it increased Bax protein in Aspc1 cells. The overexpression of mPer2 suppressed Cdc2 kinase activity. Moreover, infection with AdmPer2 resulted in dose-dependent synergic cell killing effects with the anticancer agent cisplatin (CDDP) in human pancreatic cancer cells. This synergic effect might be related to the reduction of Bcl-X(L) induced by infection with AdmPer2. Our results suggest that the circadian gene Period2 may play an important role in suppression of cell proliferation in human cancer, and additionally Period2 gene expression level may influence the sensitivity to cisplatin depending on Bcl-X(L) expression level.
巻・号 29(4)
ページ 1201-9
公開日 2009-4-1
PII 29/4/1201
PMID 19414365
MeSH Adenoviridae / genetics Animals Antineoplastic Agents / therapeutic use* Apoptosis / drug effects Blotting, Western Cell Cycle / drug effects Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cell Proliferation / drug effects Cisplatin / therapeutic use* Drug Synergism Enzyme-Linked Immunosorbent Assay Flow Cytometry Humans Mice Nuclear Proteins / genetics Nuclear Proteins / metabolism* Pancreatic Neoplasms / drug therapy* Pancreatic Neoplasms / metabolism* Pancreatic Neoplasms / pathology Period Circadian Proteins RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Transcription Factors / genetics Transcription Factors / metabolism* Tumor Cells, Cultured
IF 1.994
引用数 44
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 WI-38