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评估结肠癌患者中SgK269的表达以及人脂肪间充质干细胞分泌组通过SgK269/c-Src/p-P130Cas/p-桩蛋白/p-细胞外信号调节激酶1/2信号通路对HT-29结肠癌细胞侵袭的影响。

Evaluation of SgK269 expression in colon cancer patients and the effects of hAMSCs secretome on tumor invasion through SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2 signaling pathway in HT-29 colon cancer cells.

作者信息

Safari Fatemeh, Ansari Dogaheh Fatemeh, Dadashi Haniyeh

机构信息

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

出版信息

3 Biotech. 2023 Nov;13(11):346. doi: 10.1007/s13205-023-03763-0. Epub 2023 Sep 22.

Abstract

Colon cancer is the fifth leading cause of cancer-related deaths worldwide. Stem cells have unique characteristics and are considered as a novel therapeutic platform for cancer. Sugen Kinase 269 (SgK269) is considered as an oncogenic scaffolding pseudo kinase which governs the rearranging of the cytoskeleton, cellular motility, and invasion. The aim of this study is to evaluate the expression of SgK269 in colon cancer patients and explore the therapeutic effects of human amniotic mesenchymal stromal cells (hAMSCs) on invasion and proliferation of colon cancer cells (HT-29) through analyzing SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2 signaling pathway. In this regard, we collected 30 samples from colon cancer patients and evaluated SgK269 expression using quantitative real-time PCR (qRT-PCR). Next, we employed a co-culture system using Transwell 6-well plates and after 72 h, tumor growth promotion and invasion were analyzed in hAMSCs-treated HT-29 cells through SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2/Rac signaling pathway using qRT-PCR, western blot method, MTT assay, wound healing assay, and DAPI staining. Our results showed upregulation of SgK269 in colon cancer patients. Treatment of HT-29 colon cancer cells with hAMSCs secretome can inhibit SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2/Rac signaling pathway and the resulting suppression of cell invasion and proliferation. Our results suggest that SgK269 is an important target in colon cancer therapy and MSCs secretome may be an effective therapeutic approach to inhibit colon cancer cell invasion and proliferation through SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2/Rac signaling pathway.

摘要

结肠癌是全球癌症相关死亡的第五大主要原因。干细胞具有独特的特性,被认为是一种新型的癌症治疗平台。Sugen激酶269(SgK269)被认为是一种致癌支架假激酶,它控制细胞骨架的重排、细胞运动和侵袭。本研究的目的是评估SgK269在结肠癌患者中的表达,并通过分析SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2信号通路,探讨人羊膜间充质基质细胞(hAMSCs)对结肠癌细胞(HT-29)侵袭和增殖的治疗作用。在这方面,我们收集了30例结肠癌患者的样本,并用定量实时PCR(qRT-PCR)评估SgK269的表达。接下来,我们使用Transwell 6孔板建立共培养系统,72小时后,通过qRT-PCR、蛋白质印迹法、MTT法、伤口愈合试验和DAPI染色,利用SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2/Rac信号通路分析hAMSCs处理的HT-29细胞中的肿瘤生长促进和侵袭情况。我们的结果显示结肠癌患者中SgK269表达上调。用hAMSCs分泌组处理HT-29结肠癌细胞可抑制SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2/Rac信号通路,并由此抑制细胞侵袭和增殖。我们的结果表明,SgK269是结肠癌治疗的一个重要靶点,间充质干细胞分泌组可能是一种有效的治疗方法,可通过SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2/Rac信号通路抑制结肠癌细胞的侵袭和增殖。

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