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

IF 3.1 4区 医学 Q3 IMMUNOLOGY Immunity, Inflammation and Disease Pub Date : 2024-09-10 DOI:10.1002/iid3.70004
Qiang Guo, Xin-Yuan Wang, Yan-Chang Zhai, Yong-Wei Dong, Qing-Si He
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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.

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奥沙利铂激活 P53/miR-34a/survivin 轴,抑制胃癌细胞进展
引言 本研究旨在确定 P53/microRNA-34a(miR-34a)/survivin 通路如何促进奥沙利铂诱导的(L-OHP)胃癌细胞抑制作用。 方法 选取 BGC-823 胃癌细胞,检测其在不同浓度和时间段的 L-OHP 处理后的存活率。测定细胞中 miR-34a、P53 和存活素的表达水平。 结果 在 12 小时组和 24 小时组中,药物浓度为 15 μg/cm²(两组的 p 均为 0.005)会显著降低细胞活力。与对照组相比,24 小时组的 miR-34a mRNA 表达量、P53 mRNA 表达量和蛋白表达量均明显增加(分别为 p = .0324、p = .0069、p = .0260),但存活素 mRNA 和蛋白表达量明显低于对照组(分别为 p = .0338 和 p = .0032)。与对照组相比,miR-34a 过表达组的胃癌细胞明显减少(p = .0020),P53 mRNA 和蛋白表达明显增加(分别为 p = .0080 和 p = .0121),survivin mRNA 和蛋白表达明显减少。(分别为 p = .0213 和 p = .0069)。 结论 奥沙利铂通过上调 miR-34a、激活上游 P53 基因的表达和驱动 BGC-823 胃癌细胞中 survivin 的下调(P53/miR-34a/survivin 轴)来抑制肿瘤的生长、侵袭和转移。
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来源期刊
Immunity, Inflammation and Disease
Immunity, Inflammation and Disease Medicine-Immunology and Allergy
CiteScore
3.60
自引率
0.00%
发文量
146
审稿时长
8 weeks
期刊介绍: Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology
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