国产阿克拉霉素A的体内外抗肿瘤作用

国产阿克拉霉素A(aclacinomycin;ACM-A)能明显抑制体外培养小鼠白血病P₃₈₈和人体胃癌SGC-7901细胞的生长。在0.01 μg/ml浓度时能抑制65.4%的克隆形成,ED₅₀为0.0085μg/ml。ACM-A对白血病小鼠有显著治疗作用,延长小鼠生命时间143%,并有半数小鼠获得治疗。对Ehrlich腹水癌和肉瘤-180也有较强的抑制作用,对肉瘤-180的作用与adriamycin相似。ACM-A主要抑制³H-TDR和。H-UR分别参人人体胃癌细胞的DNA和RNA;大剂量时对蛋白质合成也有影响。P₃₈₈细胞实验中证明ACM-A对DNA合成的抑制程度与adriamycin相似,低于daunomycin。

IN VIVO AND IN VITRO ANTITUMOR ACTIVITIES OF ACLACINOMYCIN A MADE IN CHINA

Aclacinomycin A (aclarubicin; ACM-A), an anthracycline antibiotic, is produced by the culture of Streptomyces galileus isolated from a soil specimen collected in Shanghai.Experiments demonstrated that ACM-A exhibited a significant cytotoxicity against murine leukemia P₃₈₈ and human stomach carcinoma cells (SGC-7901) in vitro. ACM-A was shown to suppress the clonal growth of P₃₈₈ stem cells with an ID₅₀ of approximately 0.0085 μg/mh In transplantable tumor system, ACM-A 1.25～3.0 mg/kg ip prolonged the life-span of mice bearing P₃₈₈ leukemia or Ehrlich carcinoma, and cured mice bearing P₃₈₈ leukemia by 56.3%. ACM-A also inhibited the growth of solid sarcoma-180 in mice. ACM-A exerted the same degree of inhibitory action on ³H-TdR incorporation into DNA as adriamycin and less than daunomycin in cultured P₃₈₈ cells. It also inhibited ³H-uridine and ³H-leucine incorporation into RNA and protein, respectively. The ip acute LD₅₀ of ACM-A was found to be 32.1 mg/kg in BDF₁ mice.