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[辅酶Q10在癌症化疗中的应用——关于增强隐蔽化合物作用的实验研究,特别是在与免疫增强剂联合化疗中的应用]

[Coenzyme Q10 in cancer chemotherapy--experimental studies on augmentation of the effects of masked compounds, especially in the combined chemotherapy with immunopotentiators].

作者信息

Kokawa T, Shiota K, Oda K, Okubo S, Okamoto Y, Okubo H

出版信息

Gan To Kagaku Ryoho. 1983 Mar;10(3):768-74.

PMID:6881995
Abstract

Immunopotentiators may mitigate the depression of immunological function caused by the cancer itself or by chemotherapeutics. However, it has been found that these immunopotentiators reduce the metabolic activity of the host against drugs, including "masked" chemotherapeutics, which might be activated by metabolization in the body. Reported here is the result of serial experiments carried out on the activation of cyclophosphamide (CPM) in tumor-bearing animals, pretreated with phenobarbital, a drug-metabolizing enzyme inducer, and coenzyme Q10, a physiological activator of the electron transfer system in mitochondrias, in combination with immunopotentiators. Female Donryu rats (120 g body weight) implanted with Yoshida Sarcoma cells (YS) (2.5 X 10(6) i.p.) were treated with CPM (160 mg/kg X 1 i.p.), 84 hrs after implantation; the levels of the normustard-like substances (active metabolites of CPM) were serially measured. Some of the animals were also treated with PSK (125 mg/kg X 5 i.p.), a proteinpolysaccharide immunopotentiator obtained from mycelia of the Coriolus vesicolor, or with OK-432 (10 KE/kg X 5 i.m.), a streptococcal immunopotentiator. The results obtained were as follows: The blood levels of the normustard-like substances were lowered, i.e. the CPM activation was depressed in the YS-bearing rats and the depression was markedly intensified by PSK or OK-432 administration. Phenobarbital (40 mg/kg X 3 i.p.) or coenzyme Q10 (5 mg/rat X 5 i.p.) administration could mitigate the depression of the blood levels caused by the immunopotentiators, and the combination of phenobarbital with coenzyme Q10 could recover the blood levels up to those of the YS-bearing control rats, or even higher. YS-implanted (i.p.) rats treated with CPM+ immunopotentiators+coenzyme Q10 survived longer than those treated with CPM+immunopotentiators. These findings suggest the usefulness of coenzyme Q10 for the enhancement of cancer immunochemotherapy using masked compounds combined with immunopotentiators; all the more so, because coenzyme Q10 has also an immuno-stimulating effect, moreover, it presents almost no side effects in clinical application.

摘要

免疫增强剂可能会减轻由癌症本身或化疗药物引起的免疫功能抑制。然而,已经发现这些免疫增强剂会降低宿主对药物的代谢活性,包括“隐蔽”的化疗药物,这些药物可能会在体内通过代谢而被激活。本文报道了在荷瘤动物中进行的一系列实验结果,这些动物预先用苯巴比妥(一种药物代谢酶诱导剂)和辅酶Q10(线粒体电子传递系统的生理激活剂)进行预处理,并与免疫增强剂联合使用,以研究环磷酰胺(CPM)的激活情况。将接种吉田肉瘤细胞(YS)(2.5×10⁶个,腹腔注射)的雌性Donryu大鼠(体重120g)在接种后84小时用CPM(160mg/kg,腹腔注射1次)进行处理;连续测量去甲氮芥样物质(CPM的活性代谢产物)的水平。部分动物还用PSK(125mg/kg,腹腔注射5次)进行处理,PSK是一种从云芝菌丝体中获得的蛋白多糖免疫增强剂,或者用OK-432(10KE/kg,肌肉注射5次)进行处理,OK-432是一种链球菌免疫增强剂。得到的结果如下:去甲氮芥样物质的血药浓度降低,即荷YS大鼠中CPM的激活受到抑制,并且PSK或OK-432给药会使这种抑制明显增强。苯巴比妥(40mg/kg,腹腔注射3次)或辅酶Q10(5mg/只,腹腔注射5次)给药可以减轻免疫增强剂引起的血药浓度降低,并且苯巴比妥与辅酶Q10联合使用可以使血药浓度恢复到荷YS对照大鼠的水平,甚至更高。用CPM +免疫增强剂+辅酶Q10处理的腹腔接种YS的大鼠比用CPM +免疫增强剂处理的大鼠存活时间更长。这些发现表明辅酶Q10对于增强使用隐蔽化合物与免疫增强剂联合的癌症免疫化疗是有用的;更重要的是,因为辅酶Q10也具有免疫刺激作用,此外,它在临床应用中几乎没有副作用。

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