左归丸抗乳腺癌转移及其作用机制

邹乐兰; 刘红宁; 吕红; 徐焕军; 朱小翠; 张舟妙; 付剑江

doi:10.13422/j.cnki.syfjx.2017230085

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左归丸抗乳腺癌转移及其作用机制

药理 | 更新时间：2024-01-04

- 左归丸抗乳腺癌转移及其作用机制
- Anti-metastatic Effect of Zuoguiwan on Breast Cancer Cells and Its Mechanisms of Action
- 中国实验方剂学杂志 2017年23卷第23期页码：85-90
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金项目（81560639，81660680）;江西省自然科学基金项目（20171BAB205097）
- DOI：10.13422/j.cnki.syfjx.2017230085
  中图分类号： R285.5
- 纸质出版日期：2017
- 稿件说明：
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邹乐兰, 刘红宁, 吕红, 等. 左归丸抗乳腺癌转移及其作用机制[J]. 中国实验方剂学杂志, 2017,23(23):85-90.

ZOU Le-lan, LIU Hong-ning, LYU Hong, et al. Anti-metastatic Effect of Zuoguiwan on Breast Cancer Cells and Its Mechanisms of Action[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(23): 85-90.
邹乐兰, 刘红宁, 吕红, 等. 左归丸抗乳腺癌转移及其作用机制[J]. 中国实验方剂学杂志, 2017,23(23):85-90. DOI： 10.13422/j.cnki.syfjx.2017230085.

ZOU Le-lan, LIU Hong-ning, LYU Hong, et al. Anti-metastatic Effect of Zuoguiwan on Breast Cancer Cells and Its Mechanisms of Action[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(23): 85-90. DOI： 10.13422/j.cnki.syfjx.2017230085.

摘要

目的：观察左归丸的抗乳腺癌转移作用，探讨其作用机制。方法：采用股骨内注射法建立人乳腺癌细胞MDA-MB-231骨转移裸鼠模型，受试裸鼠随机分为空白组（蒸馏水），左归丸低、高剂量（21，42 g·kg-1）组。连续给药8周后，采用巢式聚合酶链式反应（PCR）检测裸鼠骨髓组织中人细胞角蛋白（ck19）基因的表达，确定肿瘤转移情况；采用Oris法，检测左归丸含药血清对乳腺癌细胞MDA-MB-231体外迁移能力的影响；采用重组基底膜侵袭法，观察左归丸含药血清的体外抗侵袭作用；采用Alexa Fluor488®标记的鬼笔环肽（Phalloidin）进行荧光染色，观察左归丸含药血清对乳腺癌细胞纤维型肌动蛋白（F-actin）聚合的影响；采用蛋白质印迹法（Western blot）检测左归丸含药血清对MDA-MB-231细胞甲状旁腺激素相关蛋白（PTHrP）和4型趋化因子受体（CXCR4）表达的影响。结果：与空白组比较，左归丸高、低剂量均可显著抑制小鼠骨髓组织中人ck19基因表达（P<0.01）。Oris迁移表明，左归丸含药血清可显著抑制转化生长因子-β（TGF-β）诱导的MDA-MB-231细胞迁移；重组基底膜侵袭实验显示，左归丸含药血清也可显著抑制乳腺癌细胞对重组基底膜的侵袭能力。给药组侵袭细胞数较空白组显著降低（P<0.01）。Phalloidin荧光染色结果显示，左归丸含药血清可显著抑制F-actin聚合，抑制F-actin聚合体的形成。Western blot结果表明，左归丸含药血清可显著抑制乳腺癌细胞PTHrP，CXCR4蛋白表达。结论：左归丸具有明显的抗乳腺癌骨转移作用，其机制与抑制肿瘤细胞PTHrP，CXCR4表达，从而直接抑制其体外运动活性相关。

Abstract

Objective: To investigate the anti-metastatic effect of Zuoguiwan and its mechanisms of action. Method: The bone marrow metastasis mode of nude mice was established by intra-femoral injection. The tumor-bearing mice were randomly divided into three groups:control group

low-dose Zuoguiwan (21 g·kg-1 per day) treatment group and high-dose Zuoguiwan (42 g·kg-1 per day) treatment group. After successive administration for 8 weeks

the expression of human ck19 gene was detected by nest polymerase chain reaction (PCR) assay to determine the metastatic foci of MDA-MB-231 cells in bone marrow. Oris migration assay was performed to determine the effect of Zuoguiwan-containing sera on the migration of MDA-MB-231 cells. Reconstituted basement membrane invasion assay was conducted to decide the effect of Zuoguiwan-containing sera on the invasion of MDA-MB-231 cells. F-actin polymerization was detected with Alexa Fluor® 488 phalloidin and fluorescence microscopy. The effect of Zuoguiwan-containing sera on parathyroid hormone-related protein (PTHrP) and C-X-C chemokine receptor type 4 (CXCR4) expressions in MDA-MB-231 was determined by Western blot assay. Result: Compared with control group

both low-dose Zuoguiwan group and high-dose Zuoguiwan group exhibited a significant suppression on the expression of ck19 gene in bone marrow of tumor-bearing mice (P<0.01). Data from Oris migratory assay showed that Zuoguiwan-containing sera inhibited transforming growth factor-beta (TGF-β)-induced migration in MDA-MB-231 cells significantly. It was also found that the invasive ability of MDA-MB-231 cells through reconstituted basement membrane was inhibited by Zuoguiwan-containing sera in reconstituted basement membrane invasion assay. The amount of invaded cells in Zuoguiwan-containing sera treatment groups was less than that in control group obviously (P<0.01). Data from fluorescence assay showed that Zuoguiwan-containing sera inhibited F-actin polymerization of breast cancer cells. It was also showed that Zuoguiwan-containing sera suppressed the expressions of PTHrP and CXCR4 in Western blot assay

significantly. Conclusion: Zuoguiwan has a significant anti-metastatic effect on breast cancer cells. Its mechanism of action is correlated with the suppression on motility of breast cancer cells

and the down-regulation of PTHrP and CXCR4 expressions.

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