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目的：克服肿瘤细胞的多药耐药（ＭＤＲ）。方法：用人工合成互补于ｍｄｒ１基因５′端转录起始部位的反义寡核苷酸（ＯＤＮ），直接转染耐药细胞株ＫＢ－８－５细胞，或以脂质体ｌｉｐｏｆｅｃｔｉｎ为载体进行基因转染实验，通过ＭＴＴ法检测细胞对柔红霉素（ＤＮＲ）的敏感性，流式细胞仪分析细胞内ＤＮＲ含量及免疫组化方法确定细胞表面糖蛋白（Ｐｇｐ）的表达水平。结果：ＯＤＮ可增加ＫＢ－８－５细胞内的ＤＮＲ浓度从而提高耐药细胞对ＤＮＲ的敏感性，ｌｉｐｏｆｅｃｔｉｎ进一步加强上述作用。在ＤＮＲ浓度为３．０ｍｇ／Ｌ组中，约有７４．４３％的被转染细胞对ＤＮＲ敏感而致死，基本达到药物敏感细胞株ＫＢ－３－１的水平。ＯＤＮ转染的ＫＢ－８－５细胞的Ｐｇｐ为弱阳性表达，低于阳性对照ＫＢ－８－５细胞的Ｐｇｐ表达水平。结论：ＯＤＮ的逆转作用可能与其互补结合的ｍｄｒ１ｍＲＮＡ降解或直接阻滞了Ｐｇｐ合成使其表达降低有关。
Objective: To overcome the multidrug resistance (MDR) of tumor cells. METHODS: The anti-sense oligonucleotide (ODN) complementary to the transcription initiation site of the 5′ end of the mdr1 gene was artificially synthesized and directly transfected into KB-8-5 cells, or lipofectin was used as the carrier. Gene transfection experiments were performed to determine the sensitivity of cells to daunorubicin (DNR) by MTT assay, intracellular DNR content was analyzed by flow cytometry, and the expression level of cell surface glycoprotein (Pgp) was determined by immunohistochemistry. RESULTS: ODN increased the concentration of DNR in KB-8-5 cells to increase the sensitivity of DNR to drug-resistant cells, and lipofectin further enhanced these effects. In the 3.0 mg/L DNR group, approximately 74.43% of the transfected cells were DNR-sensitive and lethal, which basically reached the level of drug-sensitive cell line KB-3-1. The Pgp of KB-8-5 cells transfected with ODN was weakly positive, lower than that of positive control KB-8-5 cells. CONCLUSION: The reversal of ODN may be related to the degradation of its complementary binding mdr1 mRNA or direct inhibition of Pgp synthesis to reduce its expression.