Tryptophan 2, 3‑dioxygenase promotes proliferation, migration and invasion of ovarian cancer cells

Mol Med Rep. 2021 Jun;23(6):445. doi: 10.3892/mmr.2021.12084. Epub 2021 Apr 13.

Abstract

Tryptophan 2,3‑dioxygenase (TDO2) is a key rate‑limiting enzyme in the kynurenine pathway and promotes tumor growth and escape from immune surveillance in different types of cancer. The present study aimed to investigate whether TDO2 serves a role in the development of ovarian cancer. Reverse transcription‑quantitative PCR and western blotting were used to detect the expression of TDO2 in different cell lines. The effects of TDO2 overexpression, TDO2 knockdown and TDO2 inhibitor on ovarian cancer cell proliferation, migration and invasion were determined by MTS, colony formation and Transwell assays. The expression of TDO2 in ovarian cancer tissues, normal ovarian tissues and fallopian tube tissues were analyzed using the gene expression data from The Cancer Genome Atlas and Genotype‑Tissue Expression project. Immune cell infiltration in cancer tissues was evaluated using the single sample gene set enrichment analysis algorithm. The present study found that RasV12‑mediated oncogenic transformation was accompanied by the upregulation of TDO2. In addition, it was demonstrated that TDO2 was upregulated in ovarian cancer tissues compared with normal ovarian tissues. TDO2 overexpression promoted proliferation, migration and invasion of ovarian cancer cells, whereas TDO2 knockdown repressed these phenotypes. Treatment with LM10, a TDO2 inhibitor, also repressed the proliferation, migration and invasion of ovarian cancer cells. The present study indicated that TDO2 can be used as a new target for the treatment of ovarian cancer.

Keywords: tryptophan 2,3‑dioxygenase; ovarian cancer; proliferation; migration; invasion.

MeSH terms

  • Carcinogenesis
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cell Transformation, Neoplastic / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kynurenine
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Tryptophan Oxygenase / genetics
  • Tryptophan Oxygenase / metabolism*
  • Tryptophan Oxygenase / pharmacology*
  • Up-Regulation

Substances

  • Kynurenine
  • Tryptophan Oxygenase

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant nos. 81572780, 81773011 and 81972648) and the Zhejiang Provincial Natural Sciences Foundation (grant nos. LZ16H160004, LY16C050004 and LY18H030008).