Effect of adenovirus-mediated mutant exogenous P27kip1 gene expression on the chemosensitivities of cholangiocarcinoma cell line.
- Author:
Jian LUO
1
;
Zhi-hua CAO
;
Min-feng LIU
;
Shi ZUO
;
Jing-qing DONG
;
Sheng-quan ZOU
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Antineoplastic Agents; pharmacology; Apoptosis; drug effects; Bile Duct Neoplasms; pathology; Bile Ducts, Intrahepatic; Cell Division; drug effects; Cell Line, Tumor; Cholangiocarcinoma; pathology; Cyclin-Dependent Kinase Inhibitor p27; genetics; pharmacology; Drug Synergism; Genetic Vectors; Humans; Transfection
- From: Chinese Journal of Surgery 2006;44(19):1349-1352
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of mutant exogenous P27(kip1) gene on chemosensitivity of human cholangiocarcinoma cell line.
METHODSThe recombinant vector was constructed and the mutant P27(kip1) gene was transfected into human cholangiocarcinoma cell line (QBC(939)). RT-PCR and Western blot were used to determine the expression of target genes. The effects of 5-fluorouracil (5-FU), mitomycin C (MMC) and cyclophosphamide (CTX) on the transfected cells were detected by assaying the apoptotic rate and growth inhibition by methabenzthiazuron (MTT) assay and flow cytometry (FCM).
RESULTSThe mutant exogenous P27(kip1) gene was expressed effectively in the cells, and the expression enhanced the apoptosis and growth inhibition of QBC(939) inducted by 5-FU, MMC and CTX. The ratio of growth inhibiting increased significantly from 41.89% (5-FU), 45.59% (MMC), 38.91% (CTX) to 56.15% (5-FU), 55.65% (MMC), 51.69% (CTX), and apoptosis index from 13.76% +/- 3.03% (5-FU), 11.76% +/- 3.99% (MMC), 10.46% +/- 2.10% (CTX) to 41.39% +/- 4.32% (5-FU), 35.94% +/- 2.71% (MMC), 34.46% +/- 2.32% (CTX) (P < 0.05).
CONCLUSIONSThe exogenous P27(kip1) gene transfer can remarkably increase the drug sensibility of the cholangiocarcinoma cells. The strategy targeted to control the cell cycle may be more effective in cancer treatment by combination of P27(kip1) gene therapy.
