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微小RNA-138通过抑制丙酮酸脱氢酶激酶1的表达降低结直肠癌对奥沙利铂的耐药性

MiR-138 Suppresses the PDK1 Expression to Decrease the Oxaliplatin Resistance of Colorectal Cancer.

作者信息

Wang Yao, Zhang Duo, Li Yao, Fang Fang

机构信息

Inspection Institute, Jilin Medical University, Jilin City, Jilin Province 132013, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Apr 29;13:3607-3618. doi: 10.2147/OTT.S242929. eCollection 2020.

DOI:10.2147/OTT.S242929
PMID:32431512
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7198439/
Abstract

BACKGROUND

Oxaliplatin is one kind of platinum-based drug. It is effective and commonly used in the treatment of colorectal cancer (CRC). However, development of acquired drug resistance is still a big obstacle during the oxaliplatin therapy. It is urgent to take strategies to decrease the oxaliplatin resistance of CRC.

MATERIALS AND METHODS

Oxaliplatin-resistant HT29 and SW480 (HT29/R and SW480/R) cells were acquired through long-term exposure to oxaliplatin by using the routine HT29 and SW480 cells. Relative glucose consumption, lactate generation and LDH activity were tested to evaluate the glycolysis of CRC cell lines. MTT assays were conducted to evaluate the differences of oxaliplatin sensitivity between HT29/R (SW480/R) cells and their parental HT29 (SW480) cells. Regulation of miR-138 on PDK1 was confirmed through qRT-PCR, Western blot and dual-luciferase reporter assays. Reactive oxygen species (ROS) levels were measured by flow cytometry.

RESULTS

HT29/R and SW480/R cells exhibited higher glucose consumption, lactate production and LDH activity compared to their parental HT29 and SW480 cells. However, oxygen consumption rate (OCR) in HT29/R and SW480/R cells is lower than that in HT29 and SW480 cells, respectively. Results of MTT assays showed that treatment with miR-138 can increase the cytotoxicity of oxaliplatin to HT29/R and SW480/R cells. Research on mechanisms showed that PDK1 was the target of miR-138. Overexpression of miR-138 can inhibit the expression of PDK1, and thus increase the OCR of HT29/R and SW480/R cells. Under the treatment of oxaliplatin, the miR-138-overexpressed HT29/R and SW480/R cells generated more amount of ROS to get into the apoptosis process.

CONCLUSION

Overexpression of miR-138 suppressed the PDK1 expression to decrease the oxaliplatin resistance of CRC.

摘要

背景

奥沙利铂是一种铂类药物。它在治疗结直肠癌（CRC）方面有效且常用。然而，获得性耐药的出现仍是奥沙利铂治疗过程中的一大障碍。采取策略降低CRC对奥沙利铂的耐药性迫在眉睫。

材料与方法

通过使用常规的HT29和SW480细胞长期暴露于奥沙利铂来获得奥沙利铂耐药的HT29和SW480（HT29/R和SW480/R）细胞。检测相对葡萄糖消耗、乳酸生成和乳酸脱氢酶（LDH）活性以评估CRC细胞系的糖酵解情况。进行MTT试验以评估HT29/R（SW480/R）细胞与其亲代HT29（SW480）细胞之间奥沙利铂敏感性的差异。通过qRT-PCR、蛋白质免疫印迹法和双荧光素酶报告基因试验证实miR-138对丙酮酸脱氢酶激酶1（PDK1）的调控作用。通过流式细胞术测量活性氧（ROS）水平。

结果

与亲代HT29和SW480细胞相比，HT29/R和SW480/R细胞表现出更高的葡萄糖消耗、乳酸产生和LDH活性。然而，HT29/R和SW480/R细胞中的氧消耗率（OCR）分别低于HT29和SW480细胞中的氧消耗率。MTT试验结果表明，用miR-138处理可增加奥沙利铂对HT29/R和SW480/R细胞的细胞毒性。机制研究表明，PDK1是miR-138的靶标。miR-138的过表达可抑制PDK1的表达，从而增加HT29/R和SW480/R细胞的OCR。在奥沙利铂处理下，miR-138过表达的HT29/R和SW480/R细胞产生更多量的ROS以进入凋亡过程。

结论

miR-138的过表达抑制PDK1表达以降低CRC对奥沙利铂的耐药性。

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本文引用的文献

1
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Adv Clin Exp Med. 2019 Nov;28(11):1459-1468. doi: 10.17219/acem/108552.
2
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Cancers (Basel). 2019 Oct 16;11(10):1576. doi: 10.3390/cancers11101576.
3
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Neoplasia. 2024 Dec;58:101076. doi: 10.1016/j.neo.2024.101076. Epub 2024 Oct 30.
4
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Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231206003. doi: 10.1177/15330338231206003.
5
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Cancer Cell Int. 2023 Oct 10;23(1):234. doi: 10.1186/s12935-023-03077-4.
6
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7
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Biomol Ther (Seoul). 2022 Sep 1;30(5):447-454. doi: 10.4062/biomolther.2022.028. Epub 2022 May 25.
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Am J Transl Res. 2019 Aug 15;11(8):5134-5149. eCollection 2019.
4
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Cell Oncol (Dordr). 2019 Dec;42(6):847-860. doi: 10.1007/s13402-019-00471-x. Epub 2019 Sep 6.
5
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Int J Mol Sci. 2018 Nov 22;19(12):3711. doi: 10.3390/ijms19123711.