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中药合剂LQ与传统化疗对小鼠模型肺癌转移及生存影响的疗效与毒性比较

Comparison of efficacy and toxicity of traditional Chinese medicine (TCM) herbal mixture LQ and conventional chemotherapy on lung cancer metastasis and survival in mouse models.

作者信息

Zhang Lei, Wu Chengyu, Zhang Yong, Liu Fang, Wang Xiaoen, Zhao Ming, Hoffman Robert M

机构信息

AntiCancer, Inc., San Diego, California, United States of America; Department of Surgery, University of California San Diego, San Diego, California, United States of America.

Department of Traditional Chinese Medicine Diagnostics, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

PLoS One. 2014 Oct 6;9(10):e109814. doi: 10.1371/journal.pone.0109814. eCollection 2014.

DOI:10.1371/journal.pone.0109814
PMID:25286158
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4186882/
Abstract

Unlike Western medicine that generally uses purified compounds and aims to target a single molecule or pathway, traditional Chinese medicine (TCM) compositions usually comprise multiple herbs and components that are necessary for efficacy. Despite the very long-time and wide-spread use of TCM, there are very few direct comparisons of TCM and standard cytotoxic chemotherapy. In the present report, we compared the efficacy of the TCM herbal mixture LQ against lung cancer in mouse models with doxorubicin (DOX) and cyclophosphamide (CTX). LQ inhibited tumor size and weight measured directly as well as by fluorescent-protein imaging in subcutaneous, orthotopic, spontaneous experimental metastasis and angiogenesis mouse models of lung cancer. LQ was efficacious against primary and metastatic lung cancer without weight loss and organ toxicity. In contrast, CTX and DOX, although efficacious in the lung cancer models caused significant weight loss, and organ toxicity. LQ also had anti-angiogenic activity as observed in lung tumors growing in nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice, which selectively express GFP in nascent blood vessels. Survival of tumor-bearing mice was also prolonged by LQ, comparable to DOX. In vitro, lung cancer cells were killed by LQ as observed by time-lapse imaging, comparable to cisplatinum. LQ was more potent to induce cell death on cancer cell lines than normal cell lines unlike cytotoxic chemotherapy. The results indicate that LQ has non-toxic efficacy against metastatic lung cancer.

摘要

与通常使用纯化化合物并旨在靶向单个分子或途径的西医不同,中药(TCM)组合物通常包含多种草药和对疗效至关重要的成分。尽管中药使用历史悠久且广泛,但很少有中药与标准细胞毒性化疗的直接比较。在本报告中,我们在小鼠模型中比较了中药复方LQ与阿霉素(DOX)和环磷酰胺(CTX)对肺癌的疗效。在皮下、原位、自发性实验性转移和血管生成小鼠肺癌模型中,LQ直接测量以及通过荧光蛋白成像抑制肿瘤大小和重量。LQ对原发性和转移性肺癌有效,且不会导致体重减轻和器官毒性。相比之下,CTX和DOX虽然在肺癌模型中有效,但会导致显著的体重减轻和器官毒性。在巢蛋白驱动的绿色荧光蛋白(ND-GFP)转基因裸鼠中生长的肺肿瘤中观察到,LQ也具有抗血管生成活性,该转基因裸鼠在新生血管中选择性表达GFP。与DOX相当,LQ也延长了荷瘤小鼠的生存期。在体外,通过延时成像观察到,LQ可杀死肺癌细胞,与顺铂相当。与细胞毒性化疗不同,LQ对癌细胞系诱导细胞死亡的作用比对正常细胞系更强。结果表明,LQ对转移性肺癌具有无毒疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff08/4186882/153e75cbc49d/pone.0109814.g009.jpg
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