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

  • Heliyon. 2023 Jun 1;9(6):e16872. doi: 10.1016/j.heliyon.2023.e16872.
Haifeng Zhang  1  2 ,  Zhenghui Jing  1  2 ,  Rong Liu  1  2 ,  Yassin Shada  2 ,  Sindhwani Shria  1  2 ,  Shiyu Cui  1  2 ,  Yuhua Ren  1  2 ,  Yuan Wei  3 ,  Liangming Li  3  4 ,  Shuang Peng  3  4
Affiliations
  • 1. Department of Pathology of Basic Medicine College, Xi'an Jiaotong University, Xi'an 710061, China.
  • 2. Institute of Genetics and Developmental Biology of Translational Medicine Institute, Xi'an Jiaotong University, Xi'an 710049, Shannxi, China.
  • 3. Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou 510500, China.
  • 4. School of Sport and Health Sciences, Guangzhou Sport University, Guangzhou 510500, China.
PMID: 37313175 DOI: 10.1016/j.heliyon.2023.e16872
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-Oxadep), maintained a similar resistant property as R-Oxa cells. The LRRC8A mRNA and protein expression were markedly increased in both R-Oxa and R-Oxadep 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.

Keywords
Colon cancer; Drug resistance; LRRC8A; Oxaliplatin; VRAC.
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