重组腺病毒载体介导人OSM 基因对胰腺癌细胞增殖的抑制作用及对裸鼠致瘤性的影响

目的　构建了含人抑瘤素M (humanoncostatinM ,hosm)基因的复制缺陷型重组腺病毒载体 ,观察其对胰腺癌细胞株BxPC3 在体外生长抑制情况及在裸鼠致瘤性改变的作用 ,为胰腺癌的基因治疗提供参考。方法　用含hosm基因的缺陷型腺病毒载体转染人胰腺癌细胞株 ,用RT PCR法检测外源hosm基因在其中的表达 ;苔盘蓝染色、细胞计数法检测ad hosm对BxPC3 的体外增殖抑制情况 ;裸鼠皮下接种转染ad hosm的BxPC3 ,观察其对肿瘤形成率的影响。结果　hosm基因在转染细胞能有效的表达。体外试验示ad hosm能明显抑制BxPC3 的生长 ,ad hosm能抑制BxPC3 在裸鼠中的成瘤作用。结论　重组腺病毒介导hosm基因表达能有效抑制BxPC3 在体外、体内的增殖 ,提示重组腺病毒介导的hosm基因治疗可能成为胰腺癌治疗的侯选方案。

Effects of induction of a human OSM gene via recombinant adenovirus on growth of human pancreatic carcinoma cells and tumorigenecity in nude mice

Objective To construct a replication-deficient recombinant adenoviral vector encoding human oncostatin M (hosm) gene and evaluate its potential for suppressing the cell growth of a pancreatic carcinoma cell line (BxPC_3) in vitro and tumorigenesis in nude mice to develop a gene therapy protocol for treatment of the pancreatic carcinoma. Methods The recombinant replication-deficient adenoviral vector encoding hosm gene was constructed by using homologous recombination modality. The expression of exogenous hosm gene in adenovirus-infected BxPC_3 cells was determined by RT-PCR. The inhibition of BxPC_3 cell proliferation by ad-hosm was determined by trapan blue exclusion cell count assay. BxPC_3 cells pretreated with ad-hosm,Ad-GFP or PBS were subcutaneously injected into the female Balb/c nude mice to investigate the tumorigenicity. Results The expected recombinant adenovirus vectors with high titer and purity were harvested. In vitro experiment showed that ad-hosm could significantly inhibit the growth of pancreatic carcinoma cells. ad-hosm could also inhibit tumorigenicity of BxPC_3 cells in nude mice. Conclusions The expression of hosm gene delivered by recombinant adenovirus is effective to inhibit the proliferation of BxPC_3 cells in vitro and in vivo. The recombinant adenovirus-mediated hosm gene therapy might be a candidate for treatment of pancreatic carcinoma.