Expression of the Multidrug Resistance Gene (MDR1) and In Vivo Intrinsic Multidrug Resistance in Human Tumor Xenografts

多药耐药基因（MDR 1）编码的膜相关P-糖蛋白（PGp）的过表达可减少多药耐药细胞的药物蓄积。然而，目前还不清楚P-GP是否是有效的肿瘤多药耐药（MDR）在体内。我们研究了34例人类肿瘤异种移植物对两种化疗药物（长春新碱，VCR;阿霉素，DOX）的体内敏感性。用临床等效剂量的药物治疗荷人肿瘤异种移植物的裸鼠。34例异种移植物中有24例（71%）对VCR和DOX均表现出固有MDR。其余10例移植瘤对VCR和DOX敏感。本文应用聚合酶链反应技术检测了34例移植瘤中MDR 1基因的表达，并对体内内源性MDR的发生机制进行了探讨。24例异种移植物中有13例（54%）显示出低强度和不同强度的MDR 1基因转录物。在10个敏感的肿瘤异种移植物中未检测到MDR 1基因表达。P-Gp的表达并不能完全解释肿瘤移植瘤内在MDR的体内机制，而P-Gp可能参与了有限数量的肿瘤移植瘤体内MDR。其他机制也有助于体内肿瘤异种移植物的内在MDR。

The overexpression of membrane associated P-qlycoprotein (PGp) encoded by the multidrug resistance gene (MDR1) decreases drug accumulation in multidrug resistant cells in vitro. However, it is unclear whether P-Gp is effective for multidrug resistance (MDR) in neoplasms in vivo. We examined the sensitivity of 34 human tumor xenografts to two chemotherapeutic drugs (Vincristine, VCR; doxorubicin, DOX) in vivo. Nude mice bearing human tumor xenografts were treated with clinical equivalent doses of the drugs. Twenty four of the 34(71%) xenografts showed intrinsic MDR both to VCR and DOX. The other 10 xenografts were sensitive in vivo to VCR and DOX. We evaluated the expression of MDR1 gene in the 34 tumor xenografts by polymerase chain reaction and discuss the mechanism(s) of in vivo intrinsic MDR. Thirteen of the 24 xenografts (54%) showed low and various intensity of MDR1 gene transcripts. No MDR1 gene expression was detected in the 10 sensitive tumor xenografts. The expression of P-Gp does not completely explain in vivo mechanisms of intrinsic MDR of tumor xenografts, whereas P-Gp may contribute to the MDR of the restricted number of tumor xenografts in vivo. Alternative mechanisms also contribute to intrinsic MDR of tumor xenografts in vivo.