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CDK 抑制逆转肝癌细胞获得性氟尿嘧啶耐药。

CDK Inhibition Reverses Acquired 5-Fluorouracil Resistance in Hepatocellular Carcinoma Cells.

机构信息

Department of the Hepato-Biliary-Pancreatic Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China.

School of Bioengineering, Hangzhou Medical College, Hangzhou, Zhejiang, China.

出版信息

Dis Markers. 2022 Mar 11;2022:6907057. doi: 10.1155/2022/6907057. eCollection 2022.

Abstract

BACKGROUND

5-Fluorouracil (5-FU) has been widely applied in treating cancers. However, its usage is largely limited in hepatocellular carcinoma (HCC), due to acquired resistance. Here, we aim to identify target proteins and investigate their roles in 5-FU sensitivity of HCC cells.

METHODS

Mass spectrometry (MS) proteomics was performed on 5-FU-resistant cell line (BEL7402/5-FU) and its parental cell line (BEL7402) with 5-FU treatment. In order to identify potential targets, we compared the proteomics between two cell line groups and used bioinformatics tools to select hub proteins from all differentially expressed proteins.

RESULTS

We finally focused on a group of cell cycle-related kinases (CDKs). By CCK8 assay, we confirmed that the CDK inhibitor significantly decreased the IC of 5-FU-resistant cells.

CONCLUSIONS

Our study verified that CDK inhibition can reverse 5-FU resistance of HCC cells.

摘要

背景

5-氟尿嘧啶(5-FU)已广泛应用于癌症的治疗。然而,由于获得性耐药,其在肝细胞癌(HCC)中的应用受到了很大限制。在这里,我们旨在确定靶蛋白,并研究它们在 HCC 细胞对 5-FU 敏感性中的作用。

方法

用 5-FU 处理 5-FU 耐药细胞系(BEL7402/5-FU)及其亲本细胞系(BEL7402),进行质谱(MS)蛋白质组学分析。为了鉴定潜在的靶点,我们比较了两组细胞之间的蛋白质组学,并使用生物信息学工具从所有差异表达蛋白中选择枢纽蛋白。

结果

我们最终关注了一组细胞周期相关激酶(CDKs)。通过 CCK8 检测,我们证实 CDK 抑制剂显著降低了耐药细胞的 5-FU 的 IC。

结论

本研究验证了 CDK 抑制可以逆转 HCC 细胞对 5-FU 的耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/092d/8933118/435594e94178/DM2022-6907057.001.jpg

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