氨氯地平对小鼠黑色素细胞瘤B16细胞自发性肺转移的抑制作用及其机制  

Inhibitory Effect of Amlodipine on Spontaneous Pulmonary Metastasis of Murine Melanoma B16 Cells and Relevant Mechanism

作　　者：张旭[1] 廖一兰[1] 孙洋[2] 孙文娟[1] 

机构地区：[1]重庆市生物化学与分子药理学重点实验室重庆医科大学药学院药理教研室,重庆400016 [2]吉林大学白求恩医学院免疫系,长春130021

出　　处：《中国生物制品学杂志》2011年第3期324-328,共5页Chinese Journal of Biologicals

基　　金：重庆医科大学自然科学基金(NSFYY200822)

摘　　要：目的研究氨氯地平对小鼠黑色素细胞瘤B16细胞自发性肺转移的抑制作用及其机制。方法将小鼠黑色素细胞瘤B16细胞接种于C57BL/6J小鼠右腹股沟皮下,2×106个/只,次日将小鼠随机分为阴性对照组(给予生理盐水0.2 ml/只,每天灌胃1次,共21 d)、氨氯地平低、中、高剂量组(分别给予氨氯地平1、3和10 mg/kg,每天灌胃1次,共21 d)和环磷酰胺组(给予环磷酰胺20 mg/kg,每2 d腹腔注射1次,共7次),观察小鼠成瘤及活动情况。于末次给药后第2天断颈处死小鼠,观察小鼠的肺转移情况及抑瘤率;体外进行血小板聚集试验及黏附试验,比较药物作用前后血小板聚集及黏附能力的差异。结果氨氯地平可抑制小鼠黑色素细胞瘤B16细胞的体内增殖、自发性肺转移、B16细胞诱导的小鼠血小板聚集以及血小板与B16细胞的黏附,且呈剂量依赖性。结论氨氯地平对小鼠黑色素细胞瘤B16细胞具有抑制体内增殖和自发性肺转移的作用,其机制可能与抑制肿瘤细胞诱导的血小板聚集及肿瘤细胞与血小板的黏附有关。Objective To investigate the inhibitory effect of amlodipine on spontaneous pulmonary metastasis of murine melanoma B16 cells as well as the relevant mechanism.Methods C57BL / 6J mice were inoculated s.c.with murine melanoma B16 cells in right inguen,2 × 106 cells for each,and divided into negative control,positive control as well as amlodipine high,moderate and low dosage groups the next day.The mice in negative control group were inoculated with physiological saline by oral route,0.2 ml for each,once a day for 21 d,while those in amlodipine low,moderate and high dosage groups with amlodipine at dosages of 1,3 and 10 mg / kg respectively.However,the mice in positive control group were injected i.p.with 20 mg / kg cyclophosphamide,once 2 days for 7 times.The tumor formations as well as activities of mice in various groups were observed.The mice were killed on the second day after the last inoculation,and observed for pulmonary metastasis of B16 cells,based on which the tumor inhibition rate was calculated.The platelet aggregation and adherence abilities before and after inoculation were compared by platelet aggregation test and adherence test in vitro respectively.Results Amlodipine showed dose-dependent inhibitory effect on the in vivo proliferation and spontaneous pulmonary metastasis of B16 cells,the platelet aggregation induced by B16 cells as well as the adherence of platelet to B16 cells.Conclusion Amlodipine inhibited the in vivo proliferation and spontaneous pulmonary metastasis of B16 cells by a potential mechanism which might be associated with inhibiting the tumor cells-induced platelet aggregation and the adherence of tumor cells to platelet.

关 键 词：钙通道阻滞药 氨氯地平 黑色素瘤 实验性 肿瘤转移 血小板 

分 类 号：R730.261[医药卫生—肿瘤]