Kowalski J, Belowski D, Madej A, Herman Z S
Department of Clinical Pharmacology, Silesian Medical Academy, Katowice, Poland.
Arch Immunol Ther Exp (Warsz). 1995;43(5-6):265-71.
We have investigated the effect of bestatin and thiorphan on growth of murine transplantable tumors, survival time, activity of natural killer (NK) cells and macrophages in mice. The injections of thiorphan at the does of 0.5 or 5 micrograms per mouse retarded tumor growth and prolonged survival period in B16 melanoma bearing animals. Pretreatment with naloxone (an unspecific antagonist of opioid receptors) blocked the tumor growth inhibition induced by the treatment with bestatin and thiorphan what could suggest a contribution of endogenous enkephalin in this antitumor effect. The percentage of mice bearing B16 melanoma tumor in the group treated with thiorphan at doses of 0.5, 5 or 50 micrograms per mouse was lower in comparison with control animals in a dose-dependent manner. The treatment with thiorphan at concentrations of 0.4-1.6 mg/ml inhibited growth of cultured in vitro B16 melanoma cell in comparison with control culture. Thiorphan added to the medium at concentration of 0.5 microgram/ml or administered 4 times at the dose of 0.5 microgram/mouse augmented NK lymphocyte activity.
我们研究了抑氨肽酶B和硫羟吗啡酮对小鼠可移植肿瘤生长、存活时间、小鼠自然杀伤（NK）细胞及巨噬细胞活性的影响。以每只小鼠0.5微克或5微克的剂量注射硫羟吗啡酮可延缓B16黑色素瘤荷瘤动物的肿瘤生长并延长生存期。用纳洛酮（阿片受体非特异性拮抗剂）预处理可阻断抑氨肽酶B和硫羟吗啡酮治疗所诱导的肿瘤生长抑制，这提示内源性脑啡肽在这种抗肿瘤效应中发挥了作用。与对照动物相比，每只小鼠分别给予0.5微克、5微克或50微克硫羟吗啡酮治疗组中携带B16黑色素瘤肿瘤的小鼠百分比呈剂量依赖性降低。与对照培养相比，浓度为0.4 - 1.6毫克/毫升的硫羟吗啡酮处理可抑制体外培养的B16黑色素瘤细胞生长。以0.5微克/毫升的浓度添加到培养基中或按0.5微克/只小鼠的剂量给药4次的硫羟吗啡酮可增强NK淋巴细胞活性。
