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LRRC8A促进结肠癌细胞中奥沙利铂耐药性的初始发展。

LRRC8A promotes the initial development of oxaliplatin resistance in colon cancer cells.

作者信息

Zhang Haifeng, Jing Zhenghui, Liu Rong, Shada Yassin, Shria Sindhwani, Cui Shiyu, Ren Yuhua, Wei Yuan, Li Liangming, Peng Shuang

机构信息

Department of Pathology of Basic Medicine College, Xi'an Jiaotong University, Xi'an 710061, China.

Institute of Genetics and Developmental Biology of Translational Medicine Institute, Xi'an Jiaotong University, Xi'an 710049, Shannxi, China.

出版信息

Heliyon. 2023 Jun 1;9(6):e16872. doi: 10.1016/j.heliyon.2023.e16872. eCollection 2023 Jun.

DOI:10.1016/j.heliyon.2023.e16872
PMID:37313175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10258452/
Abstract

Leucine-rich repeat-containing 8 A (LRRC8A) is an essential component of the volume-regulated anion channel (VRAC), which plays a vital role in cell proliferation, migration, apoptosis, and drug resistance. In this study, we investigated the effects of LRRC8A on oxaliplatin resistance in colon cancer cells. The cell viability was measured after oxaliplatin treatment with cell counting kit-8 (CCK8) assay. RNA sequencing was used to analyze the differentially expressed genes (DEGs) between HCT116 and oxaliplatin-resistant HCT116 cell line (R-Oxa) cells. CCK8 assay and apoptosis assay indicated that R-Oxa cells significantly promoted drug resistance to oxaliplatin compared with native HCT116 cells. R-Oxa cells, deprived of oxaliplatin treatment for over six months (R-Oxa), maintained a similar resistant property as R-Oxa cells. The LRRC8A mRNA and protein expression were markedly increased in both R-Oxa and R-Oxa cells. Regulation of LRRC8A expression affected the resistance to oxaliplatin in native HCT116 cells, but not R-Oxa cells. Furthermore, The transcriptional regulation of genes in the platinum drug resistance pathway may contribute to the maintenance of oxaliplatin resistance in colon cancer cells. In conclusion, we propose that LRRC8A promotes the acquisition rather than the maintenance of oxaliplatin resistance in colon cancer cells.

摘要

富含亮氨酸重复序列8A（LRRC8A）是容积调节性阴离子通道（VRAC）的重要组成部分，其在细胞增殖、迁移、凋亡和耐药性方面发挥着至关重要的作用。在本研究中，我们调查了LRRC8A对结肠癌细胞奥沙利铂耐药性的影响。在用细胞计数试剂盒8（CCK8）测定法进行奥沙利铂处理后，测量细胞活力。RNA测序用于分析HCT116细胞和奥沙利铂耐药HCT116细胞系（R - Oxa）细胞之间的差异表达基因（DEG）。CCK8测定法和凋亡测定法表明，与天然HCT116细胞相比，R - Oxa细胞显著促进了对奥沙利铂的耐药性。在超过六个月未进行奥沙利铂处理的R - Oxa细胞（R - Oxa）中，维持了与R - Oxa细胞相似的耐药特性。LRRC8A的mRNA和蛋白表达在R - Oxa细胞和R - Oxa细胞中均显著增加。LRRC8A表达的调节影响了天然HCT116细胞对奥沙利铂的耐药性，但对R - Oxa细胞没有影响。此外，铂类耐药途径中基因的转录调节可能有助于维持结肠癌细胞对奥沙利铂的耐药性。总之，我们提出LRRC8A促进结肠癌细胞对奥沙利铂耐药性的获得而非维持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/7b43ae2606fa/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/000371908863/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/f7f6edc56c45/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/c70b72a7b47f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/42549e8f53da/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/158e1a456e40/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/b2004c3fa611/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/8c920020b9cc/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/287bce6431e9/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/18b4a2612feb/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/7c20d300769d/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/7b43ae2606fa/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/000371908863/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/f7f6edc56c45/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/c70b72a7b47f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/42549e8f53da/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/158e1a456e40/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/b2004c3fa611/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/8c920020b9cc/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/287bce6431e9/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/18b4a2612feb/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/7c20d300769d/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b1/10258452/7b43ae2606fa/mmcfigs5.jpg

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