Thioredoxin domain-containing protein 9 (TXNDC9) contributes to oxaliplatin resistance through regulation of autophagy-apoptosis in colorectal adenocarcinoma

Biochem Biophys Res Commun. 2020 Apr 9;524(3):582-588. doi: 10.1016/j.bbrc.2020.01.092. Epub 2020 Feb 3.

Abstract

Colorectal cancer (CRC) is the third most commonly malignancy worldwide. The incidence of CRC is on the rise and leads to indisputable society burden due to the high cost of cancer treatments. Resistance to oxaliplatin-chemotherapy is the major cause for treatment failure and CRC-related death. In this study, we anticipated that TXNDC9 might demonstrate a protective role in oxaliplatin-resistant CRC cells. TXNDC9 was found significantly upregulated when treated with oxaliplatin. Manipulation of TXNDC9 expression largely affected the oxaliplatin-induced cell death. Moreover, TXNDC9 regulates autophagy and apoptosis in response to oxaliplatin treatment in HT29 cells via the Nrf2 pathway. Taken together, our findings explore the biological role of TXNDC9 in oxaliplatin resistance in CRC cells and may identify a novel therapeutic target to counteract drug resistance to oxaliplatin in CRC.

Keywords: Apoptosis; Autophagy; Nrf2 pathway; Oxaliplatin resistance; TXNDC9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Apoptosis* / drug effects
  • Apoptosis* / genetics
  • Autophagy* / drug effects
  • Autophagy* / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Drug Resistance, Neoplasm / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • HT29 Cells
  • Humans
  • NF-E2-Related Factor 2 / metabolism
  • Oxaliplatin / pharmacology*
  • Thioredoxins / genetics
  • Thioredoxins / metabolism*
  • Up-Regulation / drug effects

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • TXNDC9 protein, human
  • Oxaliplatin
  • Thioredoxins