title: Hypoxia enhances aggressiveness of cholangiocarcinoma cells.
abstract: Hypoxia, a common feature of solid tumors, plays a significant role in determining tumor phenotype and tumor progression. In this study, using an in-house PCR-array, we investigated phenotypic changes and differentially expressed hypoxia related genes in the KKU-M213 CCA cell line, cultured under hypoxic (1% O2) condition. Trefoil factor-1 (TFF1), a disintegrin, and metalloprotease 12 (ADAM12), integrin-alpha 5 (ITGA5) and baculoviral IAP repeat-containing 5 (BIRC5/survivin), proteins involved with cell proliferation, metastasis and apoptosis resistance, were up-regulated whereas uridine 5'-monophosphate synthase (UMPS) and S100 calcium binding protein P (S100P), involved with chemosensitivity and cell adhesion, were down-regulated. Growth arrest, apoptosis resistance to UV-irradiation and chemotherapeutic drugs (5- flourouracil, cisplatin, doxorubicin) as well as cell adhesion were thus significantly enhanced upon exposure to hypoxic condition. These findings emphasize the significance of a hypoxic state in the induction of an aggressive phenotype and suggest the potential of targeting hypoxia regulated genes to enhance the sensitivity of chemotherapeutic drug against CCA.
authors.affiliation: Department of Biochemistry, Khon Kaen University, Thailand.
authors.forename: Wunchana
authors.initials: W
authors.lastname: Seubwai
authors.forename: Ratthaphol
authors.initials: R
authors.lastname: Kraiklang
authors.forename: Chaisiri
authors.initials: C
authors.lastname: Wongkham
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma; D002945:Cisplatin / Q000627:therapeutic use; D006801:Humans
chemical_list: D002945:Cisplatin