RESUMEN
Cholangiocarcinoma is the second most common primary hepatic tumour originating from biliary tract epithelial cells with poor prognosis. Enhanced c-Myc protein expression contributes to many aspects of tumour cell biology. Although the ability of c-Myc to drive unrestricted cell proliferation and to inhibit cell differentiation had been well recognized, whether down-regulated c-Myc expression can inhibit tumour cell invasion still remains to be explored. The c-Myc ASODN (antisense oligodeoxyribonucleotide) and NSODN (nonsense oligodeoxyribonucleotide) were designed, synthesized and transfected into human QBC939 bile duct carcinoma cells using the Lipofectamine 2000 reagent. The protein expression of c-Myc was detected by Western blot. A transwell experiment was applied to evaluate the invasive capacity of the QBC939 cells. c-Myc ASODN could significantly suppress the c-Myc protein expression (P<0.05) and the invasion (P<0.01) of QBC939 cells transfected with c-Myc ASODN compared with that in the control and c-Myc NSODN-transfected group. Thus in the present study we show that down-regulation of c-Myc expression can inhibit the invasion of QBC939 cells in vitro.
Asunto(s)
Neoplasias de los Conductos Biliares/metabolismo , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/metabolismo , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Codón sin Sentido/genética , Codón sin Sentido/farmacología , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Humanos , Hígado/patología , Neoplasias Hepáticas/metabolismo , Invasividad Neoplásica , Oligodesoxirribonucleótidos Antisentido/genética , Oligodesoxirribonucleótidos Antisentido/farmacología , Proteínas Proto-Oncogénicas c-myc/genética , TransfecciónRESUMEN
To investigate risk factors for extrahepatic cholangiocarcinoma (ECC) in China. A total of 200 ECC cases and 200 matched control were included in the study. The presence of cigarette smoking, alcohol drinking, choledocholithiasis, primary sclerosing cholangitis, liver fluke infection (Clonorchis sinensis), diabetes mellitus, was investigated through clinical records. Blood from all cases was tested for hepatitis B surface antigen. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Compared with controls, ECC patients had a higher prevalence of cigarette smoking (61.0 vs. 47.0%, P=0.007), alcohol drinking (17.5 vs. 3.5%, P<0.000), and choledocholithiasis (6.0 vs. 1.0%, P=0.011). By multivariate analysis, the significant risk factors for the development of ECC were current smoking (OR=1.90, 95% CI=1.08-3.34), heavy alcohol drinking (OR=2.08, 95% CI=1.39-3.13), and choledocholithiasis (OR=6.68, 95% CI=1.48-30.27). The prevalence of hepatitis B virus infection, diabetes mellitus were not significantly different between cases and controls. These findings suggest that smoking, alcohol drinking, and choledocholithiasis are positive risk factors for the development of ECC in China.