Indoleamine-2,3-dioxygenase, an immunosuppressive enzyme that inhibits natural killer cell function, as a useful target for ovarian cancer therapy | Zendy

Dongdong Wang | Zendy; Yasushi Saga | Zendy; Hiroaki Mizukami | Zendy; Naoto Sato | Zendy; Hiroaki aka | Zendy; Hiroyuki Fujiwara | Zendy; Yuji Takei | Zendy; Shizuo Machida | Zendy; Osamu Takikawa | Zendy; Keiya Ozawa | Zendy; Mitsuaki Suzuki | Zendy

Open Access

Indoleamine-2,3-dioxygenase, an immunosuppressive enzyme that inhibits natural killer cell function, as a useful target for ovarian cancer therapy

Author(s) -

Dongdong Wang,

Yasushi Saga,

Hiroaki Mizukami,

Naoto Sato,

Hiroaki aka,

Hiroyuki Fujiwara,

Yuji Takei,

Shizuo Machida,

Osamu Takikawa,

Keiya Ozawa,

Mitsuaki Suzuki

Publication year - 2011

Publication title -

international journal of oncology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.405

H-Index - 122

ISSN - 1019-6439

DOI - 10.3892/ijo.2011.1295

Subject(s) - ovarian cancer , downregulation and upregulation , cancer research , indoleamine 2,3 dioxygenase , oncogene , biology , cancer , cancer cell , cell , small hairpin rna , cell growth , cell cycle , transfection , natural killer cell , cell culture , immunology , in vitro , cytotoxic t cell , gene knockdown , tryptophan , biochemistry , genetics , amino acid , gene

This study examined the role of the immuno-suppressive enzyme indoleamine-2,3-dioxygenase (IDO) in ovarian cancer progression, and the possible application of this enzyme as a target for ovarian cancer therapy. We transfected a short hairpin RNA vector targeting IDO into the human ovarian cancer cell line SKOV-3, that constitutively expresses IDO and established an IDO downregulated cell line (SKOV-3/shIDO) to determine whether inhibition of IDO mediates the progression of ovarian cancer. IDO downregulation suppressed tumor growth and peritoneal dissemination in vivo, without influencing cancer cell growth. Moreover, IDO downregulation enhanced the sensitivity of cancer cells to natural killer (NK) cells in vitro, and promoted NK cell accumulation in the tumor stroma in vivo. These findings indicate that downregulation of IDO controls ovarian cancer progression by activating NK cells, suggesting IDO targeting as a potential therapy for ovarian cancer.

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