Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan.
Int J Oncol. 2012 Apr;40(4):929-34. doi: 10.3892/ijo.2011.1295. Epub 2011 Dec 13.
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.
本研究探讨了免疫抑制酶吲哚胺 2,3-双加氧酶(IDO)在卵巢癌进展中的作用,以及将该酶作为卵巢癌治疗靶点的可能性。我们将靶向 IDO 的短发夹 RNA 载体转染到持续表达 IDO 的人卵巢癌细胞系 SKOV-3 中,建立 IDO 下调细胞系(SKOV-3/shIDO),以确定抑制 IDO 是否介导卵巢癌的进展。IDO 下调抑制了体内肿瘤生长和腹膜播散,而不影响癌细胞生长。此外,IDO 下调增强了癌细胞对自然杀伤(NK)细胞的体外敏感性,并促进了 NK 细胞在体内肿瘤基质中的积累。这些发现表明,下调 IDO 通过激活 NK 细胞来控制卵巢癌的进展,提示针对 IDO 可能是一种治疗卵巢癌的潜在方法。