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作 者:刘伟杰[1] 杜钢军[1] 王莹莹[1] 刘迎辉[1] 李鸿儒[1] 赵贝[1]
出 处:《中药药理与临床》2013年第2期114-118,共5页Pharmacology and Clinics of Chinese Materia Medica
基 金:河南大学省部共建项目(SBGJ090704);河南省高校青年骨干教师项目(2010GGJS-025);河南省科技厅重点攻关项目(112101310308);国家自然科学基金项目(81173094)
摘 要:目的:研究斑蝥酒制品的急性毒性,比较斑蝥酒制品对小鼠肺癌的治疗作用。方法:通过序贯法测定斑蝥酒制品的LD50,采用斑蝥不同酒制品LD50的1/3剂量对小鼠Lewis肺癌进行治疗,考察斑蝥不同酒制品对原位肿瘤、肺转移及荷瘤小鼠生存时间的影响,并通过ELISA检测荷瘤小鼠血清中LN(层粘连蛋白),PAF(血小板活化因子),TrkB(酪氨酸激酶B)和TrkA(酪氨酸激酶受体)水平以探索斑蝥可能的机制。体外MTT法比较斑蝥不同酒制品对小鼠Lewis肺癌细胞的毒性差异。结果:斑蝥经酒浸泡后随浸泡次数增加毒性明显降低,第1次浸泡的酒溶液(70mg/kg)及其浸泡后的药粉(110mg/kg)与生斑蝥(45mg/kg)有同样的抗肿瘤作用,但毒性明显减弱。与模型组比较,斑蝥酒制品明显降低荷瘤小鼠血清LN,PAF,TrkB和TrkA水平。体外试验,斑蝥酒制品的细胞毒性与体内一致,第1次酒浸泡后的溶液(100μg/ml)对肿瘤细胞的抑制作用最强。结论:斑蝥经酒浸泡后可在保持抗肿瘤活性基础上降低其毒性,其第1次酒浸液与浸泡后的药粉具有同等抗肿瘤和抗转移作用,能延长小鼠的生存时间,其抗肿瘤机制可能与降低LN,,PAF及神经营养因子受体水平相关。To study the acute toxicity of cantharides wine processed products (CWPP) and compare their therapeutic effect on lung cancer in mice. Methods: LDso of CWPP was determined by sequential application. 1/3 dose of LDs0 was used to treat Lewis lung cancer in- oculated subcutaneously in mice. The effects of different CWPP on situ tumor size, lung metastasis and survival time of tumor-bearing mice were investigate. The possible mechanism was explored by the levels of LN (laminin), PAF (platelet activating factor), TrkB (tyrosine ki- nase B) and TrkA ( receptor tyrosine kinase)in serum from tumor-bearing mice determined using ELISA. The cytotoxic difference of different CWPP was detected by MTT assay in Lewis lung cancer cells. Results: The cantharides toxicity obviously decreased following increasing in the soaking times. The wine solution(70mg/kg)and its powder from first soaked cantharis with wine(110mg/kg) had the same antitumor ac- tivity as crude cantharides(45mg/kg) but had weaker toxicity. Compared with model group, CWPP significantly reduced the levels of serum LN, PAF, TrkB and TrkA in tumor-beating mice. The cell toxicity of CWPP in vitro was similar to that in vivo, first soaked solution( 100μg/ ml ) had the strongest antitumor activity. Conclusion: Wine processed cantharides could keep the same antitumor activity as crude canthafides when its toxicity decreased. The first soaked wine solution and it powder had similar antitumor and antimetastasis, and could prolong survival time of tumor-bearlng mice. The antitumor mechanisms of cantharides might be related to reducing in LN , PAF and neurotrophic factor re- captor level.
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