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

色氨酸2,3双加氧酶促进卵巢癌细胞增殖、迁移和侵袭

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作者:Yuemei Zhao #, Fengxing Tao #, Jiayu Jiang, Lina Chen, Jizao Du, Xiaoxiao Cheng, Qin He, Shouhui Zhong, Wei Chen, Xiaoli Wu, Rongying Ou, Yunsheng Xu, Kai-Fu Tang

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.

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