膀胱癌基因治疗的实验研究：外源肿瘤坏死因子－α基因的表达及作用

Retroviral Vector-mediated TNF gene transfer and the biological behavior of bladder cancer cells

通过逆转录病毒载体将肿瘤坏死因子－α（ＴＮＦα）基因单独或与白细胞介素－６（ＩＬ－６）基因联合导入膀胱癌细胞株ＥＪ和ＢＩＵ－８７。Ｎｏｒｔｈｅｒｎ杂交证明外源基因整合至细胞内基因组，并表达相应的ｍＲＮＡ。在转染的细胞培养上清检测到ＴＮＦα活性２～１７Ｕ／ｍｌ。体外标准培养条件下细胞生长速率无明显改变，但在软琼脂中生长减慢，裸鼠致瘤性降低。细胞增殖能力降低与细胞分泌的ＴＮＦα水平直接相关。两种细胞因子联合未见明显的协同作用。

Retroviral vectors were used to introduce the TNF-a gene or TNF-a/IL-6 genes into human bladder cancer cells ( E-J、BIU-87 ). Successful gene insertion and transcription were determined by Northern hybridization. Different levels of TNF a activity of the culture supernant were detected by L929 bioassay. The growth rate of the tumor cells was not significantly suppressed by TNF gene transfer, but decreased in soft agar. Tumor formation of the TNF producers in BALB/C nude mice was obviously delayed, of which the effects revealed no difference between TNF producers and TNF a/IL-6 producers.These studies demonstrate that exogenous TNF a gene expression in baldder cancer cells suppresses the proliferative ability of the cells(not in standard culture), and suggests the possibility of introduction of the cytokine producing baldder cancer cell vaccines.