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目的：探讨重组腺病毒分导入野生型ｐ５３，ＧＭ－ＣＳＦ和Ｂ７－１基因对肿瘤化疗耐药细胞生物学行为的影响，为临床使用该重组腺病毒治疗多药耐药的肿瘤提供实验基础。方法：选用ｐ５３异常的ＫＢ－ｓ（ＶＣＲ敏感）和ＫＢ－ｖ２００（ＶＣＲ耐药）细胞作为肿瘤化疗药物敏感和耐药的模式细胞，感染携带人野生型ｐ５３，ＧＭ－ＣＳＦ和Ｂ７－１基因的重组腺病毒后，观察这两种转基因癌细胞的生物学行为（包括药物敏感性）的变化。结果：药物敏感和耐药细胞都对腺病毒易感，重组腺病毒携带的三个外源基因（ｐ５３、ＧＭ－ＣＳＦ、Ｂ７－１基因）在两种细胞中都能得到有效表达，并且能抑制它们的生长及诱导其凋亡。耐药细胞 ＫＢ－ｖ２００在转染该重组腺病毒 ４８ｈ后，其细胞膜上 Ｐｇｐ糖蛋白的泵出药物的功能却受到显著影响，表现为罗丹明１２３在其细胞内的积累增加。ＭＴＦ的实验结果也显示出其对ＶＣＲ药物敏感性的增加，裸鼠体内实验证实了感染上述重组腺病毒的ＫＢ－ｖ２００细胞的致瘤性降低，同时能增加对化疗药物ＶＣＲ的敏感性。结论：实验研究结果提示，使用该重组腺病毒并结合化疗药物，对临床治疗多药耐药的肿瘤可能会更有效。
Objective: To investigate the effects of recombinant adenovirus transfection with wild-type p53, GM-CSF and B7-1 genes on the biological behaviors of cancer chemotherapy-resistant cells, and to provide experimental basis for the clinical use of the recombinant adenovirus to treat multidrug resistant tumors. METHODS: We used p53-deficient KB-s (VCR-sensitive) and KB-v200 (VCR-resistant) cells as chemotherapeutic drugs sensitive and resistant model cells to infect human wild-type p53, GM-CSF, and B7-1 genes. After the recombinant adenovirus was observed, the biological behavior (including drug sensitivity) of the two transgenic cancer cells was observed. RESULTS: Both drug-sensitive and drug-resistant cells were susceptible to adenovirus. Three foreign genes (p53, GM-CSF, B7-1 genes) carried by recombinant adenovirus were efficiently expressed in both cells and were able to Inhibit their growth and induce their apoptosis. After 48 hours of transfection of the recombinant adenovirus with KB-v200, the function of the pumped drug of Pgp glycoprotein on the cell membrane was significantly affected, showing the accumulation of rhodamine 123 in the cell. The results of MTF also showed an increase in its sensitivity to VCR drugs. The in vivo experiments in nude mice confirmed the reduction in tumorigenicity of KB-v200 cells infected with the above recombinant adenovirus and increased sensitivity to chemotherapeutic drugs VCR. Conclusion: The results of the experimental study suggest that the use of the recombinant adenovirus combined with chemotherapeutic drugs may be more effective for clinical treatment of multidrug resistant tumors.