棒烷肽抗生素G0069A的抗肿瘤作用  

ANTITUMOR ACTIVITY OF THE CLAVAM PEPTIDE ANTIBIOTIC G0069A

作　　者：薛玉川[1] 陈文君[1] 戴洁 戚长菁[1] 甄永苏[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

出　　处：《药学学报》1997年第9期647-651,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金

摘　　要：体外用ＭＴＴ法和动物移植性肿瘤模型研究棒烷肽抗生素Ｇ００６９Ａ的抗肿瘤活性。结果表明，Ｇ００６９Ａ对多药抗药性肿瘤细胞显示高度的杀伤活性，与阿霉素、长春新碱无交叉抗药性。Ｇ００６９Ａ经ｉｖ或ｉｐ给药对小鼠肉瘤１８０和肝癌２２有显著疗效；用小鼠可耐受剂量，对肉瘤１８０和肝癌２２的抑制率分别达８７％和７４％。提示Ｇ００６９Ａ是天然来源的具有明显抗肿瘤作用的棒烷肽。Antibiotic G0069A, produced by a Streptomyces strain isolated from a soil sample collected in Yunnan Province, China, has been verified as a clavam peptide. Determined by MTT assay, G0069A showed highly potent cytotoxicity to cancer cells with multidrug resistance. The IC 50 values of G0069A to KB and KB/VCR cells were 0 60 and 0 46 μmol·L -1 , and to MCF 7 and MCF 7/ADM cells were 1 4 and 1 2 μmol·L -1 , respectively. G0069A displayed equally potent cytotoxicity to the parent cell lines and their resistant sublines. When administered by iv or ip route at tolerable doses, G0069A exhibited markedly inhibitory effect on the growth of sarcoma 180 and hepatoma 22 in mice. At dose level of 3 mg·kg -1 , iv, ×3, sarcoma 180 and hepatoma 22 were suppressed by 87%( P <0 01) and 72%( P <0 01), respectively. The results indicate that G0069A is a β lactam antibiotic showing antitumor activity.

关 键 词：抗肿瘤抗生素 棒烷肽 Β-内酰胺 多药抗药性 

分 类 号：R979.14[医药卫生—药品]