Static and ELF magnetic fields enhance the in vivo anti-tumor efficacy of cis-platin against lewis lung carcinoma, but not of cyclophosphamide against B16 melanotic melanoma
Static and ELF magnetic fields enhance the in vivo anti-tumor efficacy of cis-platin against lewis lung carcinoma, but not of cyclophosphamide against B16 melanotic melanoma
复制标题
DOI：
10.1016/s1043-6618(03)00062-8
复制
发表时间：
2003-07-01
影响因子：
9.3
通讯作者：
Eandi, A
中科院分区：
文献类型：
--
作者：
Tofani, S;Barone, D;Eandi, A
先前的工作表明，暴露于超过3 mT的静态和极低频（ELF）磁场（MF）会减缓皮下移植的人类肿瘤的生长动力学。在免疫缺陷小鼠中，降低其转移能力并延长小鼠存活时间。在本文报道的实验中，免疫活性小鼠荷小鼠刘易斯肺癌（LLC）或B 16黑色素性黑素瘤暴露于MF，并分别用两种常用的抗癌药物：顺二氨二氯铂（cis-platin）和N，N-双（2-氯乙基）四氢-2H-1，3，2-氧氮磷杂环-2-胺2-氧化物（环磷酰胺）治疗。实验终点为生存时间。用顺铂（3 mg/kg i. p.）MF作用时间明显长于顺铂或MF作用时间，与10 mg/kg腹腔注射MF的作用时间相叠加，表明MF与药物治疗有协同作用。相反，当用环磷酰胺（50 mg/kg i. p.）没有观察到协同作用，存活曲线与单独用药物处理的小鼠完全相同。与仅给予两种已知药物的小鼠相比，在单独暴露于MF或与顺铂或环磷酰胺沿着治疗的任何小鼠中均未观察到临床体征或毒性。在用顺铂治疗的小鼠中发现MF的协同作用的可能解释可能是铂离子刺激自由基产生，并且MF增强活性氧产生，从而引起肿瘤细胞膜渗透性的变化，积极影响药物吸收。或者，或除此之外，ME（C）2003 Elsevier Science Ltd.已证明，通过局部产生自由基可提高顺铂转化为能够与DNA结合的活性物质的速率。保留所有权利。
Previous works showed that exposure to static and extremely low frequency (ELF) magnetic fields (MF) over 3 mT slows down the growth kinetics of human tumors engrafted s.c. in immunodeficient mice, reducing their metastatizing power and prolonging mouse survival. In the experiments reported here, immunocompetent mice bearing murine Lewis Lung carcinomas (LLCs) or B 16 melanotic melanomas were exposed to MF and treated respectively with two commonly used anti-cancer drugs: cis-diamminedichloroplatinum (cis-platin) and N,N-bis (2-chloroethyl)tetra-hydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide (cyclophosphamide). The experiment endpoint was survival time. The survival time of mice treated with cis-platin (3 mg/kg i.p.) and exposed to MF was significantly (P < 0.01) longer than that of mice treated only with cis-platin or only exposed to MF, superimposing that of mice treated with 10 mg/kg i.p. of the drug, showing that MF act synergically with the pharmacological treatment. On the contrary, when mice treated with cyclophosphamide (50 mg/kg i.p.) were exposed to MF no synergic effects were observed, the survival curve being exactly the same as that of mice treated with the drug alone. No clinical signs or toxicity were seen in any of the mice exposed to MF alone or along with cis-platin or cyclophosphamide treatment, compared to mice given only the two known drugs.A possible explanation for the synergic effect of MF being found in mice treated with cis-platin could be that the platinum ion stimulates radical production and that MF enhance active oxygen production bringing about changes in tumor cell membrane permeability, influencing positively the drug uptake. Alternatively, or in addition to this, it has been demonstrated that the rate of conversion of cis-platin to reactive species able to bind to DNA, is increased by localized production of free radicals by ME (C) 2003 Elsevier Science Ltd. All rights reserved.