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奥沙利铂通过激活 P53/miR-34a/survivin 轴抑制胃癌细胞的进展。

Oxaliplatin activates P53/miR-34a/survivin axis in inhibiting the progression of gastric cancer cells.

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Baotou Medical College, Baotou, China.

Department of Gastrointestinal Surgery, Qi Lu Hospital of Shandong University, Jinan, China.

出版信息

Immun Inflamm Dis. 2024 Sep;12(9):e70004. doi: 10.1002/iid3.70004.

Abstract

INTRODUCTION

The purpose of this research was to determine how the P53/microRNA-34a (miR-34a)/survivin pathway contributes to oxaliplatin-induced (L-OHP) cell inhibition in gastric cancer.

METHODS

The BGC-823 gastric cancer cells were selected, and we examined their viability following treatment with L-OHP at different concentrations and time periods. The expression levels of miR-34a, P53, and survivin in the cells were determined.

RESULTS

In the 12- and 24-h groups, drug concentration of 15 μg/cm² (p < .005 in both) significantly lowered cell viability. In comparison to the control group, miR-34a mRNA expression, P53 mRNA expression, and protein expression were all significantly greater in the 24-h group (p = .0324, p = .0069, p = .0260, respectively), but survivin mRNA and protein expressions were significantly lower than those in the control group (p = .0338, p = .0032, respectively). There was a significant decrease in gastric cancer cells in the miR-34a overexpression group (p = .0020), a significant increase in P53 mRNA and protein expression compared to the control group (p = .0080, p = .0121, respectively), and a significant decrease in survivin mRNA and protein expression compared to the control group. (p = .0213, p = .0069, respectively).

CONCLUSION

Oxaliplatin inhibits tumor growth, invasion, and metastasis by upregulating miR-34a, activating the expression of the upstream P53 gene, and driving the downregulation of survivin (P53/miR-34a/survivin axis) in BGC-823 gastric cancer cells.

摘要

简介

本研究旨在探讨 P53/微小 RNA-34a(miR-34a)/生存素通路在奥沙利铂(L-OHP)诱导的胃癌细胞抑制中的作用。

方法

选择 BGC-823 胃癌细胞,检测不同浓度和时间 L-OHP 处理后细胞活力。检测细胞中 miR-34a、P53 和生存素的表达水平。

结果

在 12 和 24 小时组中,药物浓度为 15μg/cm²(均 p<0.005)显著降低细胞活力。与对照组相比,24 小时组 miR-34a mRNA 表达、P53 mRNA 表达和蛋白表达均显著升高(p=0.0324、p=0.0069、p=0.0260),而 survivin mRNA 和蛋白表达显著降低(p=0.0338、p=0.0032)。与对照组相比,miR-34a 过表达组的胃癌细胞显著减少(p=0.0020),P53 mRNA 和蛋白表达显著升高(p=0.0080、p=0.0121),survivin mRNA 和蛋白表达显著降低(p=0.0213、p=0.0069)。

结论

奥沙利铂通过上调 miR-34a、激活上游 P53 基因表达、下调 survivin(P53/miR-34a/survivin 轴),抑制 BGC-823 胃癌细胞的肿瘤生长、侵袭和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f716/11386343/8692f7ca650f/IID3-12-e70004-g004.jpg

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