Effects of Treg cells and IDO on human epithelial ovarian cancer cells under hypoxic conditions.
The aim of the present study was to explore the effect of hypoxia on ovarian cancer. A total of 6 samples were analyzed: SKOV3‑IP cells (ovarian cancer cell line); SKOV3‑IP and regulatory T (Treg) cells; SKOV3‑IP and cytotoxic T lymphocytes (CTLs); SKOV3‑IP and natural killer (NK) cells; SKOV3‑IP co-cultured with CTLs and Treg cells; and SKOV3‑IP co-cultured with Treg cells and NK cells. The expression of indoleamine 2,3‑dioxygenase (IDO) was detected by reverse transcription-polymerase chain reaction (RT‑PCR) and western blot analysis. An enzyme‑linked immunosorbent assay (ELISA) was used to detect the concentration of transforming growth factor‑β (TGF‑β), interferon‑γ (IFN‑γ), interleukin‑2 (IL‑2), interleukin‑10 (IL‑10), and perforin. Moreover, ovarian cancer cell apoptosis and invasive ability were examined using flow cytometry and a Transwell chamber assay. IDO expression was significantly reduced in hypoxia and enhanced by Treg cells. Treg cells inhibited the IL‑2, IFN‑γ and perforin secretion, and significantly (P<0.05) increased the IL‑10 and TGF‑β levels. The effects of Treg cells were enhanced with prolongation of the cell exposure to hypoxic conditions. In addition, Treg cells attenuated the promotive effect of CTLs and NK cells on cancer cell apoptosis. In addition, Treg cells significantly increased the SKOV3‑IP invasive ability (P=0.00109) under hypoxic conditions. Our results suggest that IDO and Treg cells may serve as important therapeutic targets for patients with ovarian cancer.
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200090, P.R. China.
Jun
J
Liu
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200090, P.R. China.
Haiyan
H
Zhang
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200090, P.R. China.
Luoqi
L
Jia
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200090, P.R. China.
Hong
H
Sun
D017209:Apoptosis; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase