Antitumor activity and immunomodulatory effects of the intraperitoneal administration of Kanglaite in vivo in Lewis lung carcinoma
Antitumor activity and immunomodulatory effects of the intraperitoneal administration of Kanglaite in vivo in Lewis lung carcinoma
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DOI：
10.1016/j.jep.2012.07.025
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发表时间：
2012-09-28
影响因子：
5.4
通讯作者：
Yuan, Yong-Fang
中科院分区：
文献类型：
--
作者：
Pan, Pei;Wu, Yan;Yuan, Yong-Fang
本研究的目的：康莱特（KLT）是一种有效的抗肿瘤药物，与化疗、放疗或手术联合使用时效果良好。材料与方法：C57 BL/6小鼠刘易斯肺癌模型分为4组：对照组（C）、顺铂组（DDP 1 mg/kg）、低剂量组（6.25ml/kg体重[L]）和高剂量组（12.5ml/kg体重[H]）。T细胞增殖通过mu测定来确定。采用免疫印迹法检测核因子-κ B（NF-κ B）、抑制因子-κ B α（I-κ B α）、I-κ B激酶（IRK）和表皮生长因子受体（EGFR）水平。结果：腹腔注射KLT可明显抑制刘易斯肺癌的生长，L组和H组的脾指数明显高于C组。KLT以剂量依赖性方式刺激T细胞增殖。KLT以6.25或12.5 ml/kg剂量给药，以剂量依赖性方式降低细胞核中NF-κ B的水平，KLT显著降低肿瘤细胞胞质和总体中I κ B α、IKK和EGFR的表达。结论：康莱特对C57 BL/6小鼠刘易斯肺癌有明显的抗肿瘤和免疫刺激作用。除了细胞因子如IL-2和EGFR外，这些可能影响NF-κ B/I κ B表达的调节。进一步的工作需要研究相关的信号通路的影响，但我们的研究结果表明，KLT可能是一个有前途的抗肿瘤药物的临床应用。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Aims of the study: Kanglaite (KLT) is a useful antitumor drug with proven effects when combined with chemotherapy, radiotherapy or surgery. We hypothesize that KLT has antitumor activity and immunomodulatory effects in Lewis lung carcinoma.Materials and methods: C57BL/6 mice with Lewis lung carcinoma were divided into four groups: the control group (C), cisplatin group (1 mg/kg, DDP), low KLT group (6.25 ml/kg body weight [L] and high KLT group (12.5 ml/kg body weight [H]). T cell proliferation was determined by the mu assay. Nuclear factor-kappa B (NF-kappa B), inhibitor kappa B alpha (I kappa B alpha), I kappa B kinase (IRK) and epidermal growth factor receptor (EGFR) levels were measured by western blotting. An enzyme-linked immunosorbent assay was used to analyze the expression of interleukin-2 (IL-2).Results: Intraperitoneal KLT significantly inhibited the growth of Lewis lung carcinoma, and the spleen index was significantly higher in the L and H groups than in the C group. KLT stimulated T cell proliferation in a dose-dependent manner. Treatment with KLT at either 6.25 or 12.5 ml/kg decreased the level of NF-kappa B in the nucleus in a dose-dependent manner, and KLT markedly decreased the expression of I kappa B alpha, IKK and EGFR in the cytoplasm of tumor cells and overall. IL-2 was significantly increased in the supernatant of splenocytes in the H group.Conclusions: These results demonstrate that KLT has pronounced antitumor and immunostimulatory activities in C57BL/6 mice with Lewis lung carcinoma. These may affect the regulation of NF-kappa B/I kappa B expression, in addition to cytokines such as IL-2 and EGFR. Further work needs to investigate the relevant signaling pathway effects, but our findings suggest that KLT may be a promising antitumor drug for clinical use. (C) 2012 Elsevier Ireland Ltd. All rights reserved.