化疗提高肿瘤细胞表面趋化因子受体表达促进间充质干细胞的归巢

潘琳; 吴杰; 修金; 李丰华

doi:10.3971/j.issn.1000-8578.2016.09.004

化疗提高肿瘤细胞表面趋化因子受体表达促进间充质干细胞的归巢

Chemotherapy Promotes Mesenchymal Stem Cells Homing by Enhancing Cytokine Receptors Expression on Tumor Cells

摘要

摘要:
目的研究化疗造成的肿瘤细胞损伤促进间充质干细胞迁移的能力及机制。
方法 CCK-8法检测常用化疗药在HepG2和MCF-7细胞中的IC₅₀值，IC₂₀和IC₅₀浓度的药物短暂处理细胞后用Transwell检测肿瘤细胞培养上清对间充质干细胞的趋化作用；Real-time PCR和Western blot方法验证相关趋化因子受体的表达水平变化，免疫组织化学法研究间充质干细胞在肿瘤部位的分布情况。
结果 CCK-8法检测ADR与5-Fu对不同来源的肿瘤细胞有明显杀伤作用。Transwell检测显示仅IC₂₀浓度的5-Fu或ADR处理肿瘤细胞后可促进HUMSCs的迁移。Real-time PCR和Western blot结果显示体外化疗处理后HepG2细胞表面CCR6分子和MCF-7细胞表面CXCR4分子的基因和蛋白表达水平明显升高。免疫组织化学结果证明体内化疗后间充质干细胞向受损部位迁移明显增多。
结论化疗造成的肿瘤细胞损伤能提高肿瘤细胞表面趋化因子受体CCR6、CXCR4的表达，促进间充质干细胞向肿瘤部位归巢。

Abstract:
Objective To investigate the mechanism of human mesenchymal stem cells (MSCs) homing to damage tissues caused by chemotherapy.
Methods The IC₂₀ and IC₅₀ of chemotherapy were detected by CCK-8 assay. The MSCs migration driven by tumor cells treated with IC₂₀ or IC₅₀ ADR or 5-Fu was examined by Transwell assay. The CCR6 or CXCR4 expression was measured by real-time PCR and Western blot. The MSC distribution in tumor tissues was detected by immunohistochemistry assay.
Results ADR and 5-Fu had obvious killing ability to tumor cells. The migration activity of MSCs was increased with IC₂₀ 5-Fu or ADR treatment by Transwell detection. The treatment of ADR or 5-Fu increased the expression of CCR6 on HepG2 and CXCR4 on MCF-7 in vitro. We also observed the MSCs migration increasing in vivo with ADR treatment by immunohistochemical method.
Conclusion Tissue damage caused by chemotherapy can accumulate more MSCs around the tumor with increasing the cytokines receptor CCR6 and CXCR4 expression on tumor cells.

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