新型黑麦酮酸D衍生物D69抗乳腺癌活性研究

目的研究一种来源于海洋微生物次级代谢产物的新型黑麦酮酸D衍生物D69对人乳腺癌的体内外抑制活性,并初步探讨其分子机理。方法通过镜下观察以及MTT比色法检测D69的细胞毒作用,构建人乳腺癌裸鼠移植瘤模型研究D69体内抗肿瘤活性。结果 D69对人乳腺癌细胞系MDA-MB-435和ZR-75-30的生长具有显著的抑制作用,且呈剂量依赖性增强。其对MDA-MB-435和ZR-75-30细胞半数抑制浓度（IC50）分别为0.031μmol/L和0.036μmol/L,而对人永生化乳腺上皮细胞HMEC的抑制作用较低,IC50为0.686μmol/L。人乳腺癌裸鼠移植瘤模型验证D69能显著抑制在体肿瘤的生长。结论 D69可能是一种潜在的乳腺癌化疗药物的先导化合物。

Potent anti-breast cancer effects of a novel secalonic acid D analog D69 derived from marine microbes

Objective To investigate the in vitro and in vivo anti-breast cancer activity of D69,a novel member of secalonic acid family,which was derived from marine commensal microorganisms.Methods The inhibitory effects of D69 on growth of breast cancer cell lines and the human mammary epithelial cell line were determined by MTT assay.In addition,the in vivo antineoplastic effect of D69 on BALB/c-nude mice bearing human breast cancer cell line MDA-MB-435 was investigated.Results The IC50 values of D69 on MDA-MB-435 and ZR-75-30 cell lines after 48 h treatment were 0.031 μmol/L and 0.036 μmol/L,respectively.In contrast,inhibition of the growth of the immortalized breast epithelial cells,HMEC by D69,with an IC50 of 0.686 μmol/L,was far milder than that of the inhibition on human breast cancer cells.Treatment with D69 markedly suppressed the growth of Sarcoma xenograft in syngeneic BALB/c-nude mice in a time-dependent manner,and the reduction in tumor growth rate was significant in xenografts treated with 200 μg/kg D69.Conclusion These data suggested that D69 might be used as a promising chemotherapeutical agent for treatment of breast cancer and other solid cancers.