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目的：为了深入了解十六烷基磷酸胆碱（ＨｅＰＣ）在长期应用中是否产生耐药，通过长期诱导使ＫＢ细胞对ＨｅＰＣ产生耐药，研究耐药株ＫＢｒ的耐药特性，为其应用提供依据。方法：耐药株的建立采用低浓度ＨｅＰＣ缓慢诱导，逐步增加浓度，直至ＫＢ细胞产生明显耐药；应用ＭＴＴ法比较ＫＢ细胞与ＫＢｒ细胞对不同化疗药物的ＩＣ５０值；用ＲＴＰＣＲ检测ｍｄｒｌ，ＭＲＰ和ＧＳＴｐｉ的ｍＲＮＡ；用免疫细胞化学方法检测Ｐ糖蛋白（Ｐｇｐ）表达。结果：ＫＢ细胞经过ＨｅＰＣ７０周的长期诱导，产生耐药性，耐药倍数为３２倍。ＫＢｒ对长春新碱和秋水仙素有显著的交叉耐药，而对柔红霉素、５氟尿嘧啶、氮芥、卡氮芥、放线菌素Ｄ以及足叶乙甙（ＶＰ１６）无明显的交叉耐药性。ＫＢｒ细胞具ｍｄｒｌ基因和Ｐｇｐ蛋白的阳性表达，ＭＲＰ和ＧＳＴｐｉ基因为阴性表达。结论：通过长期诱导ＫＢ细胞产生对ＨｅＰＣ的耐药，耐药株对长春新碱和秋水仙素有交叉耐药，ｍｄｒｌ基因和Ｐｇｐ高表达可能与耐药有关。
OBJECTIVE: To investigate whether long-term use of cetylphosphocholine (HePC) produces resistance and to induce KB cells to develop resistance to HePC by long-term induction and to study the drug resistance of KBr, and to provide its application in accordance with. Methods: The drug-resistant strains were induced slowly with low concentration of HePC and gradually increased until the KB cells were significantly drug-resistant. The IC50 values of different chemotherapeutic drugs were compared between KB cells and KBr cells by MTT assay. The mdrl, MRP and GST pi mRNA; P-glycoprotein (Pgp) expression was detected by immunocytochemistry. Results: KB cells were induced by long-term HePC70 weeks and developed drug resistance with a multiple of 32 fold. KBr had a significant cross-resistance to vincristine and colchicine, but no effect on daunorubicin, 5-fluorouracil, nitrogen mustard, carmustine, actinomycin D and etoposide Significant cross-resistance. KBr cells with mdrl gene and Pgp protein positive expression, MRP and GST pi gene was negative expression. CONCLUSION: The long-term induction of KB cells produces resistance to HePC. The resistant strains are cross-resistant to vincristine and colchicine. The high expression of mdrl gene and Pgp may be related to drug resistance.