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hAMSCs 外泌体通过下调 SgK269、E-钙黏蛋白、波形蛋白和 snail 的表达对 Panc1 胰腺癌细胞的潜在治疗作用。

Potential therapeutic effects of hAMSCs secretome on Panc1 pancreatic cancer cells through downregulation of SgK269, E-cadherin, vimentin, and snail expression.

机构信息

Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran.

Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran.

出版信息

Biologicals. 2022 Apr;76:24-30. doi: 10.1016/j.biologicals.2022.02.001. Epub 2022 Feb 23.

Abstract

Pancreatic cancer is one of the leading causes of death from cancer worldwide. The current treatment options for pancreatic cancer are unsuccessful and thereby, finding novel and more effective therapeutic strategies is urgently required. Stem cells-based therapies are currently believed to be a potential promising option in cancer therapy. Herein, we are interested in evaluating the therapeutic effects of human amniotic mesenchymal stromal cells (hAMSCs) secretome on tumor growth suppression and EMT inhibition in Panc1 pancreatic cancer cells using 2D and 3D cell culture models. For this purpose, we employed a co-culture system using 6-well Transwell plates with a pore diameter of 0.4 μm. After 72 h treatment of Panc1 cancer cells with hAMSCs, the expression of c-Src, EGFR, SgK269, E-cadherin, Vimentin, Snail transcriptional factor, Bax, Bcl2, and caspase 3 was analyzed by quantitative real-time PCR (qRT-PCR) and Western blot methods. Our results showed significant reduction in tumor cell growth and motility through downregulation of c-Src, EGFR, SgK269, E-cadherin, Vimentin, and Snail transcriptional factor expression in Panc1 pancreatic cancer cells. The induction of cellular apoptosis was also found. Our finding supports the idea that the secretome from hAMSCS has therapeutic effects on cancer cells.

摘要

胰腺癌是全球癌症死亡的主要原因之一。目前胰腺癌的治疗选择并不成功,因此迫切需要寻找新的、更有效的治疗策略。基于干细胞的治疗方法目前被认为是癌症治疗的一种有前途的选择。在这里,我们有兴趣评估人羊膜间充质基质细胞(hAMSCs)分泌组对 Panc1 胰腺癌细胞肿瘤生长抑制和 EMT 抑制的治疗效果,使用 2D 和 3D 细胞培养模型。为此,我们采用了一种共培养系统,使用孔径为 0.4μm 的 6 孔 Transwell 板。用 hAMSCs 处理 Panc1 癌细胞 72 小时后,通过定量实时 PCR(qRT-PCR)和 Western blot 方法分析 c-Src、EGFR、SgK269、E-钙粘蛋白、波形蛋白、Snail 转录因子、Bax、Bcl2 和 caspase 3 的表达。我们的结果表明,通过下调 Panc1 胰腺癌细胞中的 c-Src、EGFR、SgK269、E-钙粘蛋白、波形蛋白和 Snail 转录因子的表达,肿瘤细胞的生长和迁移能力显著降低。还发现了细胞凋亡的诱导。我们的发现支持 hAMSCS 的分泌组对癌细胞具有治疗作用的观点。

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