1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulating IDO expression and re-activating im
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(2020) 21:67
RESEARCH ARTICLE
Open Access
1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via down-regulating IDO expression and re-activating immune cells function Huihan Ma1, Qian Qin1, Jiaqing Mi1 and Qinmei Feng2*
Abstract Background: The indoleamine 2, 3-dioxygenase (IDO) inhibitor 1-methyl-tryptophan (1-MT) is currently being used in clinical trials in patients with relapsed or refractory solid tumors by inhibiting tumor immune escape. A greater understanding of IDO activity is required to begin to understand the molecular mechanism by which drugs work. This study was conducted to investigate of the clinical significance of 1-methyl-tryptophan (1-MT) in treating carboplatin-resistant (CBP-resistant) ovarian cancer and its mechanism of action. Methods: Using a medium dose, intermittent treatment method, a clinically relevant CBP-resistant human ovarian cancer cell line (SKOV3/CBP) was established. SKOV3/CBP cells were treated with normal serum (control) or 1-MT (0.25 ng/mL) for 4 h (SKOV3/CBP + 1-MT). Cell proliferation, invasion and IDO expression in SKOV3, SKOV3/CBP and SKOV3/CBP + 1-MT cells were determined by MTT assays, Matrigel invasion chambers assays and ELISAs, respectively. The half-maximal inhibitory concentration (IC50) and resistance index (RI) were also calculated. The killing ability of the NK cells and CD8+ T cells co-cultured with SKOV3, SKOV3/CBP and SKOV3/CBP + 1-MT cells were determined by LDH activity assays and the INF-γcounting method. Results: The SKOV3/CBP cell line displayed an increased IC50 compared to the SKOV3 cell line (P < 0.05) under CBP treatment. Treatment with 1-MT significantly decreased the IC50 and RI of SKOV3/CBP cells. Furthermore, 1-MT treatment not only reduced the invasion ability, but also suppressed IDO expression in the drug-resistant SKOV3/ CBP + 1-MT cell line as compared to the SKOV3/CBP cell line. Furthermore, 1-MT enhanced the killing ability of NK cells and the amount of INF-γsecreted from CD8+ T cells which were co-cultured with the SKOV3/CBP cell line. Conclusion: Our data suggested that 1-MT inhibits the invasion of CBP-resistant ovarian cancer cells via downregulation of IDO expression which leads to re-activation of immune cell function. We provide a conceptual foundation for the clinical development of 1-MT as an anti-tumor immunomodulator for chemotherapy resistant ovarian cancer patients. Keywords: Ovarian cancer, Indoleamine 2, 3-dioxygenase (IDO), 1-methyl-tryptophan (1-MT), Chemotherapy resistant
* Correspondence: [email protected] 2 Department of Gynecology Medicine, People’s Hospital Affiliated to Shanxi Medical University, No. 56 Xinjian Nan Lu street, Yingze District, Taiyuan 030000, Shanxi Province, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate
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