| ZHU Dong-ming,ZHANG Ke-jun,LI De-chun,ZHU Xue-feng,YANG Yong.Radiosensitization effect of recombinant adenoviral-mediated PUMA gene on pancreatic carcinoma cells[J].Chinese Journal of Radiological Medicine and Protection,2009,29(1):27-30 |
| Radiosensitization effect of recombinant adenoviral-mediated PUMA gene on pancreatic carcinoma cells |
| Received:July 28, 2008 |
| DOI：10.3760/cma.j.issn.0254-5098.2009.01.008 |
| KeyWords:Recombinant adenovirus p53 up-regulated modulator of apoptosis gene Gene therapy Radiotherapy Pancreatic neoplasm |
| FundProject:卫生部科学研究基金资助项目(WKJ2004-2-011) |
| Author Name | Affiliation | E-mail | | ZHU Dong-ming | Department of General Surgery, First Affiliated Hospital, Soochow University, Suzhou 215006, China | | | ZHANG Ke-jun | Department of General Surgery, First Affiliated Hospital, Soochow University, Suzhou 215006, China | | | LI De-chun | Department of General Surgery, First Affiliated Hospital, Soochow University, Suzhou 215006, China | SZ4304DCL@sina.com | | ZHU Xue-feng | Department of General Surgery, First Affiliated Hospital, Soochow University, Suzhou 215006, China | | | YANG Yong | Department of General Surgery, First Affiliated Hospital, Soochow University, Suzhou 215006, China | |
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| Abstract:: |
| Objective To study the effect of PUMA gene mediated by recombinant adenovirus vector combined with radiation on the pancreatic carcinoma.Methods The PANC-1 cells were infected with Ad-PUMA (MOI=10, 50 and 100, respectively) for 48 h. The expression of PUMA mRNA and protein was detected by RT-PCR and Western blot, respectively. PANC-1 cells were divided into 4 groups: control group, transfection group, irradiation group and combined treatment group. The cell growth inhibition rate and apoptotic rate of PANC-1 cells were assessed by MTT assay and flow cytometry. Human pancreatic carcinomas were transplanted subcutaneously in nude mice, which were randomized into 4 groups: control group, transfection group, irradiation group and combined treatment group. Tumor growth rate and apoptotic index at different time points were recorded in 35 days.Results The expression of PUMA mRNA and protein was increased with the increase of MOI of Ad-PUMA, which was does-dependant (MOI=10, mRNA=0.46±0.02, protein=0.75±0.09; MOI=50, mRNA=1.12±0.09, protein =1.01±0.18; MOI=100, mRNA=1.50±0.08, protein=1.80±0.15; P<0.05). The proliferation of PANC-1 cells was suppressed significantly when transfected by Ad-PUMA in a dose-dependent manner(r=-0.986?55), which was more significant combined with radiation (r=-0.971?26,P<0.05). Meanwhile, the apoptotic rate was increased in the same manner [for pre- and post-irradiation,which was (45.4±5.26)% and (73.2±6.62)%, respectively,P<0.05]. From 7 to 35d after PUMA gene transfection and radiotherapy, the tumor growth was significantly slower than those of irradiation group, transfection group and control group [35 d after therapy, the volume of tumor was (19.82±6.45)mm3, (39.5±9.23)mm3, (33.6±10.3)mm3 and (52.0±11.43)mm3, respectively, P<0.05]. And the apoptotic index was increased in the same manner (AI=0.43±0.05, 0.29±0.10, 0.24±0.05 and 0.00±0.00, respectively, P<0.05).Conclusion Recombinant adenoviral-mediated PUMA gene combined with irradiation could increase the cell-killing effect on pancreatic carcinoma. It is better than that of either one kind of therapy. |
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