棒烷肽抗生素G0069A的抗肿瘤作用

ANTITUMOR ACTIVITY OF THE CLAVAM PEPTIDE ANTIBIOTIC G0069A

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。

Abstract: 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 IC₅₀ values of G0069A to KB and KB/VCR cells were 0.60 and 0.46μmol·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. }