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覃妮, 刘怡江, 王万平, 黄丽银, 覃文晖, 胡正国, 陆世银.白花蛇舌草多糖调节CXCL12/CXCR4轴对乳腺癌细胞增殖、迁移和侵袭的影响[J].湖南中医药大学学报英文版,2024,44(5):778-784.[Click to copy
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| 白花蛇舌草多糖调节CXCL12/CXCR4轴对乳腺癌细胞增殖、迁移和侵袭的影响 |
| 覃妮,刘怡江,王万平,黄丽银,覃文晖,胡正国,陆世银 |
| (柳州市中医医院(柳州市壮医医院)药学部, 广西 柳州 545026;柳州市中医医院(柳州市壮医医院), 中药(壮瑶药) 制剂研发重点实验室, 中药(壮瑶药)制剂开发工程技术研究中心, 广西 柳州 545026;柳州市中医医院 (柳州市壮医医院)肿瘤科, 广西 柳州 545026) |
| 摘要: |
| 目的 探讨白花蛇舌草多糖（Hedyotis diffusa Willd. Polysaccharide，HDP）对乳腺癌MDA-MB-231细胞增殖、迁移和侵袭的影响以及对CXCL12/CXCR4轴的调控机制。方法 将乳腺癌细胞分为对照组，CXCL12/CXCR4抑制剂组（AMD 3100组），HDP低、中、高剂量组（HDP-L组、HDP-M组、HDP-H组），HDP高剂量+CXCL12组（HDP-H+CXCL12组）；通过CCK-8检测细胞增殖情况；划痕实验、Transwell实验分别测定细胞的迁移和侵袭能力；Western blot分析细胞中上皮钙黏蛋白（E-cadherin）、波形蛋白（Vimentin）、CXCL12、CXCR4蛋白的表达；建立BALB/c-nu雌性裸鼠MDA-MB-231异种移植瘤模型并观察各组肿瘤生长情况，采用HE染色观察裸鼠移植瘤细胞的形态学特征。结果 与对照组相比，AMD 3100组和HDP各剂量组细胞增殖活性、迁移和侵袭数以及Vimentin、CXCL12、CXCR4蛋白表达显著抑制（P<0.05，P<0.01），而E-cadherin蛋白表达水平明显升高（P<0.01）；与HDP-H组相比，HDP-H+CXCL12组细胞的增殖活力、迁移和侵袭数以及Vimentin、CXCL12、CXCR4蛋白表达水平明显升高（P<0.01），E-cadherin蛋白表达水平被显著抑制（P<0.01）。此外，动物实验表明，与模型组相比，AMD 3100组和HDP各剂量组的肿瘤重量明显降低（P<0.05，P<0.01）；与HDP-H组相比，HDP-H+CXCL12组裸鼠肿瘤重量明显增加（P<0.01）；HE染色显示，AMD 3100组和HDP各干预组肿瘤组织坏死与凋亡细胞增多。结论 HDP可以通过抑制CXCL12/CXCR4轴进而抑制MDA-MB-231细胞的增殖、迁移及侵袭。 |
| 关键词: 白花蛇舌草多糖 乳腺癌 异种移植瘤 CXCL12/CXCR4轴 迁移 侵袭 |
| DOI：10.3969/j.issn.1674－070X.2024.05.009 |
| Received:August 24, 2023 |
| 基金项目:广西自然科学基金项目（2020GXNSFBA297032）；广西中医药大学自然科学基金面上项目（2020MS055）；柳州市科技攻关与新产品试制（2020NBAA0802）。 |
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| Effects of Hedyotis diffusa polysaccharide on proliferation, migration, and invasion of breast cancer cells by regulating CXCL12/CXCR4 axis |
| QIN Ni, LIU Yijiang, WANG Wanping, HUANG Liyin, QIN Wenhui, HU Zhengguo, LU Shiyin |
| (Department of Pharmacy, Liuzhou Hospital of Chinese Medicine(Liuzhou Hospital of Zhuang Medicine), Liuzhou, Guangxi 545026, China;Preparations, Engineering Technology Research Center for the Development of Chinese Medicine(Zhuang and Yao) Preparations, Liuzhou Key Laboratory for Preparation Development of Chinese Medicine(Zhuang and Yao), Liuzhou Hospital of Chinese Medicine(Liuzhou Hospital of Zhuang Medicine), Liuzhou, Guangxi 545026, China;Department of Oncology, Liuzhou Hospital of Chinese Medicine(Liuzhou Hospital of Zhuang Medicine), Liuzhou, Guangxi 545026, China) |
| Abstract: |
| Objective To study the effects of Hedyotis diffusa Willd. Polysaccharide (HDP) on proliferation, invasion, and migration of breast cancer cells MDA-MB-231 and the regulatory mechanism of HDP on CXCL12/CXCR4 axis. Methods Breast cancer cells MDA-MB-231 were assigned into control group, CXCL12/CXCR4 inhibitor group (AMD 3100 group), and low-, medium-, and high-dose HDP groups (HDP-L group, HDP-M group and HDP-H group), and HDP-H+CXCL12 group (HDP-H+CXCL12 group). CCK-8 was used to determine cell proliferation. Scratch assay and Transwell assay were applied to evaluate the cell migration and invasion ability. Western blot was employed to examine the protein expressions of E-cadherin, Vimentin, CXCL12, and CXCR4. MDA-MB-231 transplanted tumor model of BALB /c-nu female nude mice were established and the tumor growth of mice in each group was observed. HE staining was used to observe the morphological changes of transplanted tumor cells in nude mice. Results Compared with the control group, the cell proliferation activity, migration, and invasion number, as well as the expression levels of Vimentin, CXCL12, and CXCR4 proteins in AMD 3100 group and HDP groups of various doses decreased, while the expression level of E-cadherin protein distinctly increased (P<0.05, P<0.01). Compared with the HDP-H group, the cell proliferation, migration, and invasion number, as well as the expression levels of Vimentin, CXCL12, and CXCR4 proteins in HDP-H+CXCL12 group were enhanced (P<0.01), while the expression level of E-cadherin protein decreased (P<0.01). Additionally, in xenograft tumor experiments, compared with the control group, the tumor weight of AMD 3100 group and HDP groups of various doses were significantly lower (P<0.05, P<0.01); the tumor weight of HDP-H+CXCL12 group was significantly higher (P<0.01). HE staining showed the increased necrosis and apoptosis of tumor tissue cells in each intervention group of AMD 3100 and HDP. Conclusion HDP may inhibit the proliferation, migration, and invasion of MDA-MB-231 cells by regulating CXCL12/CXCR4 axis. |
| Key words: Hedyotis diffusa polysaccharide breast cancer xenograft tumor CXCL12/CXCR4 axis migration invasion |
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