Open Access

Downregulation of indoleamine-2,3-dioxygenase in cervical cancer cells suppresses tumor growth by promoting natural killer cell accumulation

  • Authors:
    • Naoto Sato
    • Yasushi Saga
    • Hiroaki Mizukami
    • Dongdong Wang
    • Suzuyo Takahashi
    • Hiroaki Nonaka
    • Hiroyuki Fujiwara
    • Yuji Takei
    • Shizuo Machida
    • Osamu Takikawa
    • Keiya Ozawa
    • Mitsuaki Suzuki
  • View Affiliations

  • Published online on: August 23, 2012     https://doi.org/10.3892/or.2012.1984
  • Pages: 1574-1578
  • Copyright: © Sato et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

This study examined the role of the immunosuppressive enzyme indoleamine-2,3-dioxygenase (IDO) in cervical cancer progression and the possible use of this enzyme for cervical cancer therapy. We analyzed IDO protein expression in 9 cervical cancer cell lines (SKG-I, -II, -IIIa, -IIIb, SiHa, CaSki, BOKU, HCS-2 and ME-180) stimulated with interferon-γ. IDO expression was observed in all cell lines except for SKG-IIIb. We transfected the human cervical cancer cell line CaSki that constitutively expresses IDO with a short hairpin RNA vector targeting IDO, and established an IDO-downregulated cell line to determine whether inhibition of IDO mediates cervical cancer progression. IDO downregul­ation suppressed tumor growth in vivo, without influencing cancer cell growth in vitro. Moreover, IDO downregulation enhanced the sensitivity of cervical 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 cervical cancer progression by activating NK cells, suggesting IDO as a potential therapy for cervical cancer.
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November 2012
Volume 28 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Sato N, Saga Y, Mizukami H, Wang D, Takahashi S, Nonaka H, Fujiwara H, Takei Y, Machida S, Takikawa O, Takikawa O, et al: Downregulation of indoleamine-2,3-dioxygenase in cervical cancer cells suppresses tumor growth by promoting natural killer cell accumulation. Oncol Rep 28: 1574-1578, 2012.
APA
Sato, N., Saga, Y., Mizukami, H., Wang, D., Takahashi, S., Nonaka, H. ... Suzuki, M. (2012). Downregulation of indoleamine-2,3-dioxygenase in cervical cancer cells suppresses tumor growth by promoting natural killer cell accumulation. Oncology Reports, 28, 1574-1578. https://doi.org/10.3892/or.2012.1984
MLA
Sato, N., Saga, Y., Mizukami, H., Wang, D., Takahashi, S., Nonaka, H., Fujiwara, H., Takei, Y., Machida, S., Takikawa, O., Ozawa, K., Suzuki, M."Downregulation of indoleamine-2,3-dioxygenase in cervical cancer cells suppresses tumor growth by promoting natural killer cell accumulation". Oncology Reports 28.5 (2012): 1574-1578.
Chicago
Sato, N., Saga, Y., Mizukami, H., Wang, D., Takahashi, S., Nonaka, H., Fujiwara, H., Takei, Y., Machida, S., Takikawa, O., Ozawa, K., Suzuki, M."Downregulation of indoleamine-2,3-dioxygenase in cervical cancer cells suppresses tumor growth by promoting natural killer cell accumulation". Oncology Reports 28, no. 5 (2012): 1574-1578. https://doi.org/10.3892/or.2012.1984