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C 基因诱导的 LP1 促进人胃癌细胞系 SGC-7901 自噬、凋亡并降低转移。

LP1 from C Induces Autophagy, Apoptosis and Reduces Metastasis in Human Gastric Cancer Cell Line SGC-7901.

机构信息

Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.

State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, E-208 West Campus, Dalian 116024, China.

出版信息

Int J Mol Sci. 2018 Sep 30;19(10):2986. doi: 10.3390/ijms19102986.

Abstract

Present study aimed to elucidate the anticancer effect and the possible molecular mechanism underlying the action of Latcripin 1 (LP1), from the mushroom strain C against gastric cancer cell lines SGC-7901 and BGC-823. Cell viability was measured by Cell Counting Kit-8 (CCK-8); morphological changes were observed by phase contrast microscope; autophagy was determined by transmission electron microscope and fluorescence microscope. Apoptosis and cell cycle were assessed by flow cytometer; wound-healing, transwell migration and invasion assays were performed to investigate the effect of LP1 on gastric cancer cell's migration and invasion. Herein, we found that LP1 resulted in the induction of autophagy by the formation of autophagosomes and conversion of light chain 3 (LC3I into LC3II. LP1 up-regulated the expression level of autophagy-related gene (Atg7, Atg5, Atg12, Atg14) and Beclin1; increased and decreased the expression level of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins respectively, along with the activation of Caspase-3. At lower-doses, LP1 have shown to arrest cells in the S phase of the cell cycle and decreased the expression level of matrix metalloproteinase MMP-2 and MMP-9. In addition, it has also been shown to regulate the phosphorylation of one of the most hampered gastric cancer pathway, that is, protein kinase B/mammalian target of rapamycin (Akt/mTOR) channel and resulted in cell death. These findings suggested LP1 as a potential natural anti-cancer agent, for exploring the gastric cancer therapies and as a contender for further in vitro and in vivo investigations.

摘要

本研究旨在阐明来自 菌株 C 的 Latcripin 1(LP1)对胃癌细胞系 SGC-7901 和 BGC-823 的抗癌作用及其可能的作用机制。通过 Cell Counting Kit-8(CCK-8)测定细胞活力;相差显微镜观察形态变化;透射电镜和荧光显微镜观察自噬。通过流式细胞仪评估细胞凋亡和细胞周期;进行划痕愈合、Transwell 迁移和侵袭实验,以研究 LP1 对胃癌细胞迁移和侵袭的影响。在此,我们发现 LP1 通过自噬体的形成和 LC3I 向 LC3II 的转化导致自噬的诱导。LP1 上调自噬相关基因(Atg7、Atg5、Atg12、Atg14)和 Beclin1 的表达水平;分别增加和减少促凋亡(Bax)和抗凋亡(Bcl-2)蛋白的表达水平,并激活 Caspase-3。在较低剂量下,LP1 可使细胞停滞在细胞周期的 S 期,并降低基质金属蛋白酶 MMP-2 和 MMP-9 的表达水平。此外,它还可以调节蛋白激酶 B/雷帕霉素靶蛋白(Akt/mTOR)通路,这是阻碍胃癌进展的最严重通路之一,从而导致细胞死亡。这些发现表明 LP1 可能是一种潜在的天然抗癌药物,可用于探索胃癌的治疗方法,并作为进一步的体外和体内研究的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b084/6213425/dcc7b162ffdb/ijms-19-02986-g001.jpg

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