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新建立的高三尖杉酯碱（HHT）耐药细胞系的鉴定及耐药机制

Characterization of the Newly Established Homoharringtonine- (HHT-) Resistant Cell Lines and Mechanisms of Resistance.

作者信息

Li Fenglin, Ling Qing, Hu Chao, Wang Huafeng, Ye Wenle, Li Xia, Zhang Xiang, Lin Xiangjie, Wei Wenwen, Huang Xin, Qian Yu, Zhuang Haihui, Jin Jie, Lu Ying

机构信息

Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, China.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

出版信息

J Oncol. 2022 Aug 30;2022:2813938. doi: 10.1155/2022/2813938. eCollection 2022.

DOI:10.1155/2022/2813938
PMID:36081671
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9448541/
Abstract

Homoharringtonine- (HHT-) based HHT, aclarubicin, and cytarabine (HAA) induction regimen is the first-line therapy for nonelder acute myeloid leukemia (AML) patients in China. However, drug resistance is a new challenge, and little attention has been devoted to excavating resistant mechanisms. This study used the classic method to construct six HHT-resistant cell lines with a gradually increasing resistance index (RI) to discover HHT drug resistance mechanisms dynamically. After HHT resistance, the cell growth rate decreased, cell cycle delayed, and P-glycoprotein (p-gp, CD243) expression levels increased. Furthermore, we explored the changes in transcriptomics between HHT-sensitive and HHT-resistant cells using RNA-sequence. Through Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and hub gene analyses, we found that immune activity, especially G-protein coupled receptor (GPR) and related molecules, may mediate HHT resistance. Moreover, Calcitonin Receptor-Like (CALCRL) and Protein Subunit Alpha I1 (GNAI1), which belong to GPRs, were stimulated in HHT-resistant cell strains in vitro and vivo, indicating that they may play a critical role in HHT resistance. In addition, these two genes have prognostic significance for AML patients. Taken together, we successfully constructed HHT-resistant cell lines with dynamic RIs and explored the resistance mechanisms, which will help identify new drugs for HHT-resistant AML patients.

摘要

高三尖杉酯碱（HHT）联合阿克拉霉素及阿糖胞苷（HAA）诱导方案是中国非老年急性髓系白血病（AML）患者的一线治疗方案。然而，耐药性是一个新的挑战，目前对挖掘耐药机制的关注较少。本研究采用经典方法构建了6株对HHT耐药指数（RI）逐渐升高的耐药细胞系，以动态发现HHT耐药机制。HHT耐药后，细胞生长速率降低，细胞周期延迟，P-糖蛋白（p-gp，CD243）表达水平升高。此外，我们利用RNA测序探索了HHT敏感细胞和HHT耐药细胞之间的转录组学变化。通过京都基因与基因组百科全书（KEGG）、基因本体论（GO）和枢纽基因分析，我们发现免疫活性，尤其是G蛋白偶联受体（GPR）及其相关分子，可能介导HHT耐药。此外，属于GPRs的降钙素受体样蛋白（CALCRL）和G蛋白亚基α I1（GNAI1）在体外和体内的HHT耐药细胞株中均受到刺激，表明它们可能在HHT耐药中起关键作用。此外，这两个基因对AML患者具有预后意义。综上所述，我们成功构建了具有动态RI的HHT耐药细胞系并探索了耐药机制，这将有助于为HHT耐药的AML患者识别新的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/166cfdcd6107/JO2022-2813938.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/3549fe258387/JO2022-2813938.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/9a98ddec3dfe/JO2022-2813938.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/8a2cbdc1b114/JO2022-2813938.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/1004d5527cc9/JO2022-2813938.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/166cfdcd6107/JO2022-2813938.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/3549fe258387/JO2022-2813938.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/9a98ddec3dfe/JO2022-2813938.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/8a2cbdc1b114/JO2022-2813938.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/137b1d238de9/JO2022-2813938.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/1004d5527cc9/JO2022-2813938.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7f/9448541/166cfdcd6107/JO2022-2813938.006.jpg

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2
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3
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