力达霉素烯二炔发色团对肝癌的实验治疗

Experimental therapeutic effects of the enediyne chromophoreof lidamycin against hepatoma

目的研究力达霉素发色团对肝癌的实验治疗。方法采用体内接种肿瘤法研究力达霉素发色团对小鼠肝癌22或裸鼠人肝癌Bel-7402的抗肿瘤作用。结果力达霉素发色团在肿瘤接种24h后1次静脉给药能明显抑制小鼠肝癌22的生长,当剂量达4.6、9.2、18.3μg k/g时,抑制率分别为59%、81%、85%。力达霉素发色团在接种肿瘤后72h给药的抑瘤效果不如接种后24h的效果强。力达霉素发色团L(DC)和力达霉素L(DM)均能抑制裸鼠肝癌Bel-7402肿瘤的生长。接种后d27,具有相同克分子数的LDC(18.5μgk/g)和LDM(250μgk/g)的抑瘤率分别为51.1%和45.9%,抑瘤效果相当。LDC对肿瘤生长的抑制作用存在剂量-效应关系。结论力达霉素发色团在动物体内能抑制小鼠肝癌和人裸鼠肝癌的生长,是力达霉素产生生物学作用的主要活性部分。

Objective To study the in vivo antitumor activity of the enediyne chromophore （LDC） of lidamycin. Methods After dissociation of lidamycin （LDM） molecule, the experimental therapeutic effects of the chromophore were determined by transplantable hepatoma 22 （H22） in mice and human hepatoma Bel-7402 xenografts in athymic mice. Results Administrated 24 hrs after tumor transplantation with single intravenous injection at doses of 4.6 μg/kg, 9.2 μg/kg and 18.3 μg/kg, LDC markedly suppressed the growth of H22 in mice by 59%, 81% and 85%, respectively. The inhibitory potency of LDC administrated on dl was much higher than that on d3 after tumor transplantation. LDC and LDM suppressed the growth of hepatoma Bel-7402 xenografts in athymic mice. On the equivalent molar dosage level, the inhibition rates by LDC （18.5 μg/kg） and LDM （250 μg/kg） were 51.1% and 45.9%, respectively. LDC inhibited the tumor growth of H22 and Bel-7402 xenografts in a dose dependent manner. Conclusion LDC showed effective against murine human transplantable hepatoma and human hepatoma xenograft. The therapeutic efficacy of LDC was comparable to that of LDM.