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    外泌体PFN1促进胃癌细胞增殖和迁移的机制研究

    Exosome PFN1 promotes the proliferation and migration of gastric cancer cells and related mechanisms

    • 摘要: 目的 探讨肿瘤细胞外泌体肌动蛋白调节蛋白-1(PFN1)对胃癌细胞增殖、迁移的影响及其作用机制。方法 使用实时荧光定量PCR和免疫印迹法检测正常胃细胞和胃癌细胞中PFN1 mRNA和蛋白表达水平。采用CCK8实验、细胞克隆实验、划痕实验和Transwell实验评估PFN1对胃癌细胞活力以及增殖、迁移及侵袭能力的影响。采用流式细胞术检测PFN1对胃癌细胞凋亡的影响。结果 PFN1在胃癌组织和胃癌细胞中表达量异常升高(P<0.001)。过表达PFN1的胃癌细胞活力增加,增殖、迁移和侵袭能力显著增强,过表达PFN1还可以使胃癌细胞凋亡减少(P均<0.001)。此外,胃癌细胞外泌体中的PFN1可以促进巨噬细胞的M2极化,并进一步增强胃癌细胞增殖、迁移和侵袭的能力(P均<0.001)。结论 过表达PFN1可以促进胃癌细胞的增殖、迁移和侵袭,抑制凋亡。而胃癌细胞外泌体中的PFN1可以通过刺激巨噬细胞M2极化进一步促进胃癌的发生发展。

       

      Abstract: Objective To explore the effect of tumor cell exosome profilin-1 (PFN1) on the proliferation and migration of gastric cancer cells and related mechanisms.Methods Real-time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression of PFN1 in normal gastric and gastric cancer cells. Then, CCK8 assay, cell cloning assay, scratch assay and Transwell assay were used to evaluate the effect of PFN1 on the viability, proliferation, migration and invasion of gastric cancer cells. The effect of PFN1 on the apoptosis of gastric cancer cells was detected by flow cytometry.Results The expression of PFN1 abnormally increased in gastric cancer tissues and cells (P<0.001). Over-expression of PFN1 resulted in increases in the viability, proliferation, migration and invasion of gastric cancer cells, while reducing the apoptotic rate in gastric cancer cells. Further studies indicated that PFN1 in the exosomes of tumor cells promoted the M2 polarization of macrophages, and exosomes secreted by gastric cancer cells overexpressing PFN1 stimulated the proliferation, migration and invasion of gastric cancer cells.Conclusions Over-expression of PFN1 can promote the proliferation, migration and invasion of gastric cancer cells and reduce the rate of apoptosis. PFN1 in the exosomes of gastric cancer cells can further promote the pathogenesis of gastric cancer by stimulating M2 polarization in macrophages.

       

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