CHEMORESISTANCE RELATED TO HYPOXIA ADAPTATION IN MESOTHELIOMA CELLS FROM TUMOR SPHEROIDS.

Q3 Medicine

Experimental oncology Pub Date : 2022-08-01 DOI:10.32471/exp-oncology.2312-8852.vol-44-no-2.18045

D Endoh, K Ishii, K Kohno, N Virgona, Y Miyakoshi, T Yano, T Ishida

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引用次数: 1

Abstract

Background: Hypoxia has been noted as a key factor for induction and maintenance of cancer stemness thereby leading to therapy resistance. Three-dimensional (3D) spheroid models demonstrate a heterogeneity of hypoxic regions replicating the in vivo situation within tumors. Utilizing an established 3D spheroid model, we investigated whether extrinsic hypoxia reinforced chemoresistance in malignant pleural mesothelioma (MPM) spheroids.

Materials and methods: Tumor spheres were generated from Meso-1 (a typical human MPM cell line) cells having high spheroid-forming ability. To induce hypoxia condition, we utilized a hypoxia chamber with regulation of O2 and CO2 levels. Cell viability was estimated by a WST-8 assay. Real-time polymerase chain reaction and Western blot were performed to evaluate the expression at mRNA and protein levels.

Results: Compared with cells cultured in the two-dimensional monolayer model, tumor sphere cells showed elevated mRNA levels of cancer stemness markers (CD26, CD44 and ABCG2) and protein levels of the stemness and hypoxia adaptation markers (ABCG2, ALDH1A1 and HIFs). Correlating with this, 3D spheroid cells were more resistant to permetrexed and topotecan than the two-dimensional cells, indicative of their potential for hypoxic adaptation. Furthermore, significantly stronger resistance to both chemotherapeutic agents was observed in spheroid cells upon hypoxic challenge compared to spheroid cells under normoxia.

Conclusion: From the present data, it is concluded that hypoxia adaptation of MPM cells from tumor spheres could enhance their chemoresistance.

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来自肿瘤球体的间皮瘤细胞的化疗耐药与缺氧适应有关。

背景:缺氧已被认为是诱导和维持肿瘤干细胞从而导致治疗抵抗的关键因素。三维(3D)球体模型显示了肿瘤体内缺氧区域的异质性。利用已建立的三维球体模型，我们研究了外源性缺氧是否增强了恶性胸膜间皮瘤(MPM)球体的化疗耐药。材料和方法:肿瘤球是由具有高成球能力的Meso-1(一种典型的人MPM细胞系)细胞生成的。为了诱导缺氧，我们使用了一个氧气和二氧化碳水平调节的缺氧室。用WST-8法测定细胞活力。实时聚合酶链反应和Western blot检测mRNA和蛋白水平的表达。结果:与二维单层模型培养的细胞相比，肿瘤球细胞的肿瘤干性标志物(CD26、CD44和ABCG2) mRNA水平和干性和缺氧适应标志物(ABCG2、ALDH1A1和hfs)蛋白水平均有所升高。与此相关的是，三维球形细胞比二维细胞对透曲塞和拓扑替康的抵抗力更强，表明它们具有缺氧适应的潜力。此外，在低氧条件下，球形细胞对这两种化疗药物的耐药性明显强于正常氧条件下的球形细胞。结论:肿瘤球源MPM细胞缺氧适应可增强其化疗耐药能力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental oncology Medicine-Oncology

CiteScore

1.40

自引率

0.00%

发文量

期刊介绍： The Experimental Oncology is an English-language journal that publishes review articles, original contributions, short communications, case reports and technical advances presenting new data in the field of experimental and fundamental oncology. Manuscripts should be written in English, contain original work, which has not been published or submitted for publication elsewhere. It also implies the transfer of the Copyright from the author to “Experimental Oncology”. No part of journal publications may be reproduced, stored in a retrieval system or transmitted in any form or by any means without the prior permission of the publisher.