Digestive Cancer Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
Department of Dermato‑Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, P.R. China.
Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12084. Epub 2021 Apr 13.
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.
色氨酸 2,3-双加氧酶(TDO2)是犬尿氨酸途径中的关键限速酶,可促进不同类型癌症中的肿瘤生长和逃避免疫监视。本研究旨在探讨 TDO2 是否在卵巢癌的发生发展中发挥作用。采用逆转录-定量 PCR 和 Western blot 检测不同细胞系中 TDO2 的表达。通过 MTS、集落形成和 Transwell 检测过表达 TDO2、敲低 TDO2 和 TDO2 抑制剂对卵巢癌细胞增殖、迁移和侵袭的影响。采用癌症基因组图谱和基因型-组织表达项目的基因表达数据分析卵巢癌组织、正常卵巢组织和输卵管组织中 TDO2 的表达。采用单样本基因集富集分析算法评估肿瘤组织中免疫细胞浸润。本研究发现 RasV12 介导的致癌转化伴随着 TDO2 的上调。此外,还表明与正常卵巢组织相比,卵巢癌组织中 TDO2 上调。TDO2 过表达促进卵巢癌细胞的增殖、迁移和侵袭,而 TDO2 敲低则抑制这些表型。TDO2 抑制剂 LM10 的处理也抑制了卵巢癌细胞的增殖、迁移和侵袭。本研究表明 TDO2 可作为治疗卵巢癌的新靶点。