Traditional Chinese medicine Jianpi Bushen therapy suppresses the onset of pre-metastatic niche in a murine model of spontaneous lung metastasis
Traditional Chinese medicine Jianpi Bushen therapy suppresses the onset of pre-metastatic niche in a murine model of spontaneous lung metastasis
复制标题
中药健脾补肾疗法抑制自发性肺转移小鼠模型转移前生态位的发生
DOI：
10.1016/j.biopha.2016.12.013
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发表时间：
2017-02-01
影响因子：
7.5
通讯作者：
Wu, Jie
中科院分区：
文献类型：
--
作者：
Zhu, Xiaoyun;Zhou, Yu;Wu, Jie
背景与目的：明确的转移是胃癌患者死亡的主要原因。靶器官中转移前小生境的形成为转移的癌细胞的粘附和随后的生长提供了允许的环境。靶向转移前小生境是预防转移的潜在方法。传统的中医治疗方案--健脾补肾法已被广泛应用于临床，以增强患者的抗癌能力。本工作旨在研究JPBS对自发性肺转移小鼠胃癌模型中Rac 1、Cdc 42、SDF-1和FN肺表达的调节作用。方法：用小鼠前胃癌（MFC）细胞接种615系小鼠，诱导其自发性肺转移，然后分别用JPBS、JPBS联合5-FU、或5-FU。采用实时荧光定量PCR和免疫组织化学方法分别检测肺组织中Rac 1、Cdc 42、SDF-1和FN的基因和蛋白表达。结果：与未接种肿瘤细胞的对照组相比，模型组小鼠肺组织中Rac 1、Cdc 42、SDF-1和FN的基因和蛋白表达均显著升高。JPBS处理降低模型小鼠肺中Rac 1、Cdc 42、SDF-1和FN的蛋白表达。治疗还可以抑制血液中的SDF-1和FN。结论：Rac 1、Cdc 42、SDF-1和FN在胃癌转移前小生境的早期发生中可能发挥作用，为健脾补肾法预防和抑制胃癌转移的分子机制提供理论依据。(C)2016 Elsevier Masson SAS。All rights reserved.
Background & aim: Distinct metastasis accounts for the leading cause of mortality among patients with gastric cancer. The formation of pre-metastatic niche in the target organs provides permissive environments for the adhesion and subsequent growth of metastasized cancer cells. Targeting the pre-metastatic niche is a potential approach to prevent metastasis. Traditional Chinese medicine regimen called Jianpi Bushen therapy (JPBS) has been widely used in clinics to strengthen patients' abilities to fight cancer. The present work is aimed to study the modulating effect of JPBS on the lungs expressions of Rac1, Cdc42, SDF-1, and FN in a murine gastric cancer model showing spontaneous lung metastasis.Methods: Mice of strain 615 were inoculated with tumor cells derived from mouse forestomach carcinoma (MFC) to induce spontaneous lung metastasis, and were then treated with JPBS, JPBS combined with fluorouracil (5-FU), or 5-FU. Gene and protein expressions of Rac1, Cdc42, SDF-1, and FN in lungs were determined using real-time PCR and immunohistochemistry, respectively. Serum levels of SDF-1 and FN were also measured using ELISA.Results: Gene and protein expressions of Rac1, Cdc42, SDF-1, and FN were significantly elevated in the lungs of model mice comparing to the counterpart mice received no tumor cell inoculation. JPBS treatment reduced protein expressions of Rac1, Cdc42, SDF-1 and FN in the lungs of model mice. The treatment could also suppress SDF-1 and FN in blood. For serum SDF-1 the level was further lower in model mice treated with combination therapy of JPBS and 5-FU.Conclusion: The present work identified the potential roles of Rac1, Cdc42, SDF-1 and FN in the early onset of pre-metastatic niche of gastric cancer, and provided insights into the molecular mechanism by which Jianpi Bushen therapy prevent and suppress cancer metastasis. (C) 2016 Elsevier Masson SAS. All rights reserved.