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首页> 外文期刊>British Journal of Cancer >Factors involved in the anti-cancer activity of the investigational agents LM985 (flavone acetic acid ester) and LM975 (flavone acetic acid)
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Factors involved in the anti-cancer activity of the investigational agents LM985 (flavone acetic acid ester) and LM975 (flavone acetic acid)

机译：研究药物LM985（黄酮乙酸酯）和LM975（黄酮乙酸）的抗癌活性涉及的因素

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摘要

LM985 has been shown previously to hydrolyse to flavone acetic acid (LM975) in mouse plasma and to produce significant anti-tumour effects in transplantable mouse colon tumours (MAC). It has undergone Phase I clinical trials and dose limiting toxicity was acute reversible hypotension. Substantially higher doses of LM975 can be given clinically without dose limiting toxicity. We have investigated the activity of LM975 against a panel of MAC tumours and also the in vitro cytotoxicity of both LM985 and LM975 in two cell lines derived from MAC tumours. LM985 is considerably more cytotoxic than LM975 in vitro but increased length of exposure to LM975 results in improved activity. Single in vivo injection of LM975 showed no activity against the ascitic tumour MAC 15A, moderate activity against the s.c. poorly differentiated tumour MAC 13 and produced a significant growth delay in the well differentiated MAC 26. These latter responses were considerably enhanced by repeated injection 7 days later. Pharmacokinetic studies in mice following i.p. injection of LM985 demonstrated rapid degradation of LM985 to LM975 in the peritoneum. Length of exposure as well as drug concentration appear important factors in determining anti-tumour responses.
机译：LM985先前已显示可在小鼠血浆中水解为黄酮乙酸（LM975），并在可移植的小鼠结肠肿瘤（MAC）中产生显着的抗肿瘤作用。它已经进行了I期临床试验，剂量限制性毒性为急性可逆性低血压。临床上可以给予实质上更高剂量的LM975，而没有剂量限制的毒性。我们已经研究了针对一组MAC肿瘤的LM975的活性，以及​​在源自MAC肿瘤的两种细胞系中LM985和LM975的体外细胞毒性。 LM985在体外具有比LM975更大的细胞毒性，但是与LM975接触的时间增加导致活性提高。 LM975的单次体内注射显示对腹水肿瘤MAC 15A无活性，对s.c.中等活性。低分化肿瘤MAC 13并在高分化MAC 26中产生了显着的生长延迟。7天后重复注射大大增强了后者的反应。腹腔注射后小鼠体内的药代动力学研究注射LM985证明腹膜中LM985迅速降解为LM975。暴露时间以及药物浓度是确定抗肿瘤反应的重要因素。

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