真菌产生的新核苷转运抑制剂增强药物的抗肿瘤活性  

A FUNGUS-DERIVED NOVEL NUCLEOSIDE TRANSPORT INHIBITOR POTENTIATES THE ACTIVITY OF ANTITUMOR DRUGS

作　　者：粟俭[1] 甄永苏[1] 戚长菁[1] 陈文君[1] 

机构地区：[1]中国医学科学院,中国协和医科大学医药生物技术研究所,北京医科大学天然药物及仿生药物国家重点实验室

出　　处：《药学学报》1994年第9期656-661,共6页Acta Pharmaceutica Sinica

摘　　要：从南极土壤中分离的一株真菌所产生的抗生素Ｃ３３６８－Ｂ（ＣＢ）有较强的核苷转运抑制活性。ＣＢ显著抑制艾氏腹水癌（ＥＡＣ）细胞的胸苷和尿苷转运，ＩＣ５０分别为７．５和９．６μｍｏｌ·Ｌ－１。用克隆生成法测定，ＣＢ在本身无明显细胞毒性剂量下，能显著增强氨甲蝶呤（ＭＴＸ）、５－氟脲嘧啶（５ＦＵ）和丝裂霉素Ｃ（ＭＭＣ）等抗癌药物对人口腔鳞癌ＫＢ细胞和人肝癌ＢＥＬ－７４０２细胞的杀伤。生长抑制法结果显示，ＣＢ还能部分逆转小鼠白血病Ｌ１２１０／ＭＤＲ细胞对长春新碱（ＶＣＲ）和放线菌素Ｄ（ＡＣＤ）的抗药性。结果提示新核苷转运抑制剂ＣＢ可能应用于肿瘤联合化疗的前景。Antibiotic C3368-B(CB),identified as,3,9-dihydroxy-1-methoxy-7-methylanth-raquinone ,is produced by a fungus strain ,Chrysosporium verrucosum Tubaki ,isolated from a soilsample collected from Antarctica. CB was found to be a highly-active nucleoside transport inhibitor.By radiolabelled nucleoside assay ,CB was shown to markedly inhibit thymidine and uridine transportin Ehrlich carcinoma cells , with IC50 values of 7.5 and 9.6umol·L-1 respectively,CB showedfairly low cytotoxicity to tumor cells. The IC50 values for epidermoid cancer KB cells and hepatomaBEL-7402 cells in clonogenic assay was 77 and 69umol·L-1 .At relatively noncytotoxic concentra-tions, CB markedly enhanced the cytotoxicity of methotrexate,5-fluorouracil, mitomycin C againstKB cells and BEL-7402 cells. CB was also found to partly revers1e the multi-drug resistance tovincristine and actinomvcin D in leukemia L1210/ MDR cells. The IC50 values were reduced by4.9-fold(1.75 to 0.36umol·L-1) for vincristine and 3.3-fold(0.39 to 0.12umol·L-1) foractinomvcin D. These results suggest that CB , as a newly-found nucleoside transport inhibitor , maybe potentially useful in cancer chemotherapy.

关 键 词：核苷转运 抑制剂 抗癌药 

分 类 号：R979.1[医药卫生—药品]