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

Abstract

Tryptophan 2,3-dioxygenase (TDO 2) 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 TDO 2 serves a role in the development of ovarian cancer. Reverse transcription-quantitative PCR and western blotting were used to detect the expression of TDO 2 in different cell lines. The effects of TDO 2 overexpression, TDO 2 knockdown and TDO 2 inhibitor on ovarian cancer cell proliferation, migration and invasion were determined by MTS, colony formation and Transwell assays. The expression of TDO 2 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 TDO 2. In addition, it was demonstrated that TDO 2 was upregulated in ovarian cancer tissues compared with normal ovarian tissues. TDO 2 overexpression promoted proliferation, migration and invasion of ovarian cancer cells, whereas TDO 2 knockdown repressed these phenotypes. Treatment with LM10, a TDO 2 inhibitor, also repressed the proliferation, migration and invasion of ovarian cancer cells. The present study indicated that TDO 2 can be used as a new target for the treatment of ovarian cancer.