Burke Amy J, Garrido Pablo, Johnson Carol, Sullivan Francis J, Glynn Sharon A
1 Prostate Cancer Institute, School of Medicine, National University of Ireland Galway , Galway, Ireland .
2 Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway , Galway, Ireland .
Antioxid Redox Signal. 2017 Jun 20;26(18):1078-1090. doi: 10.1089/ars.2017.7004. Epub 2017 Mar 22.
Prostate and ovarian cancers are major contributors to cancer-related deaths worldwide. Recently, inflammation and nitrosative stress have been implicated in carcinogenesis, with the overexpression of NOS2 and concomitant release of nitric oxide (NO) associated with cancer initiation and progression. Recent Advances: An increasing body of evidence indicates an association between NOS2 expression and aggressive ovarian cancer. Research also indicates a role for NO in prostate disease pathology and prostate cancer. A therapeutic role for NOS2 inhibition and/or NO drugs exists for the treatment of both ovarian and prostate tumors.
Herein, we review the key molecular effects associated with NOS2 in ovarian and prostate cancer. NOS2 increases angiogenesis and tumor proliferation and correlates with aggressive type II ovarian tumors. NOS2 expressing tumors are sensitive to cisplatin chemotherapy, and NO may be used to sensitize cisplatin-resistant tumors to chemotherapy. NOS2 is highly expressed in prostate tumors compared to non-neoplastic prostate pathologies. NO may play a role in the development of androgen-independent prostate cancer via s-nitrosylation of the androgen receptor. Moreover, NOS2 inhibitors and NO donor drugs show therapeutic potential in ovarian and prostate cancer as single agents or dual drugs, by either inhibiting the effects of NOS2 or increasing NO levels to induce cytotoxic effects.
NOS2 and NO present new targets for the treatment of ovarian and prostate tumors. Furthermore, understanding NO-related tumor biology in these cancers presents a new means for improved patient stratification to the appropriate treatment regimen. Antioxid. Redox Signal. 26, 1078-1090.
前列腺癌和卵巢癌是全球癌症相关死亡的主要原因。最近，炎症和亚硝化应激与致癌作用有关，一氧化氮合酶2（NOS2）的过表达以及随之而来的一氧化氮（NO）释放与癌症的发生和发展相关。
越来越多的证据表明NOS2表达与侵袭性卵巢癌之间存在关联。研究还表明NO在前列腺疾病病理学和前列腺癌中发挥作用。对于卵巢和前列腺肿瘤的治疗，存在NOS2抑制和/或NO药物的治疗作用。
在此，我们综述了与NOS2在卵巢癌和前列腺癌中相关的关键分子效应。NOS2增加血管生成和肿瘤增殖，并与侵袭性II型卵巢肿瘤相关。表达NOS2的肿瘤对顺铂化疗敏感，并且NO可用于使顺铂耐药肿瘤对化疗敏感。与非肿瘤性前列腺病变相比，NOS2在前列腺肿瘤中高表达。NO可能通过雄激素受体的S-亚硝基化在雄激素非依赖性前列腺癌的发展中起作用。此外，NOS2抑制剂和NO供体药物作为单一药物或联合药物在卵巢癌和前列腺癌中显示出治疗潜力，通过抑制NOS2的作用或增加NO水平以诱导细胞毒性作用。
NOS2和NO为卵巢和前列腺肿瘤的治疗提供了新的靶点。此外，了解这些癌症中与NO相关的肿瘤生物学为改善患者分层以采用适当的治疗方案提供了新方法。《抗氧化与氧化还原信号》第26卷，第1078 - 1090页
