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

人肿瘤异种移植物中多药耐药基因（MDR1）的表达和体内内在多药耐药性

基本信息

批准号：
03670163
负责人：
TAMAOKI Norikazu
金额：
$ 1.34万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670163/
关键词：
Multidrug Resistance P-giycoprotein In vivo Chemotherapy Tumor Xenograft RT-PCR MDR1 gene P糖蛋白ヌ-ドマウス PCR

项目摘要

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.

多药耐药基因（MDR1）编码的膜相关p -糖蛋白（PGp）过表达可减少体外多药耐药细胞的药物积累。然而，目前尚不清楚P-Gp是否对体内肿瘤的多药耐药（MDR）有效。我们检测了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。携带人类肿瘤异种移植物的裸鼠用临床等效剂量的药物治疗。34例异种移植物中有24例（71%）对VCR和DOX均表现出内在的MDR。其余10例异种移植物在体内对VCR和DOX敏感。我们采用聚合酶链反应的方法对34例肿瘤异种移植物中MDR1基因的表达进行了评价，并探讨了体内内源性MDR的机制。24个异种移植物中有13个（54%）显示低强度和不同强度的MDR1基因转录本。10例肿瘤敏感移植物中未检测到MDR1基因表达。P-Gp的表达并不能完全解释肿瘤异种移植物内在耐药的体内机制，而P-Gp可能有助于体内有限数量的肿瘤异种移植物的耐药。其他机制也有助于体内肿瘤异种移植物的内在耐药。