Clinical Implications of iNOS Levels in Triple-Negative Breast Cancer Responding to Neoadjuvant Chemotherapy.
Clinical Implications of iNOS Levels in Triple-Negative Breast Cancer Responding to Neoadjuvant Chemotherapy.
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iNOS 水平在三阴性乳腺癌新辅助化疗中的临床意义
DOI：
10.1371/journal.pone.0130286
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chen B
中科院分区：
文献类型：
--
作者：
Jin Z;Wang W;Jiang N;Zhang L;Li Y;Xu X;Cai S;Wei L;Liu X;Chen G;Zhou Y;Liu C;Li Z;Jin F;Chen B
三阴性乳腺癌是一种高危乳腺癌，生存率差。迄今为止，这种类型的癌症缺乏靶向治疗。一个独特的现象是，炎性乳腺癌通常是三阴性的。然而，炎症如何影响三阴性乳腺癌的生长和对化疗的反应仍然不明确。在此，我们调查了20例三阴性乳腺癌患者肿瘤中炎症相关酶iNOS的水平，并检查了其与患者对铂类新辅助化疗反应的相关性。我们的研究表明，治疗后肿瘤细胞中iNOS水平减弱的三阴性乳腺癌患者对铂类新辅助化疗的反应优于其他三阴性乳腺癌患者。我们进一步的体外研究证实，适当水平的NO诱导增加了三阴性MDA-MB-231细胞对顺铂的耐药性。我们的数据表明，异常高水平的iNOS/NO与铂类为基础的新辅助化疗在三阴性乳腺癌中的效果较差。因此，我们建议监测iNOS水平作为三阴性乳腺癌患者对铂类新辅助化疗反应的新预测因子。此外，iNOS/NO被认为是与铂类药物联合治疗三阴性乳腺癌的潜在靶点。
Triple-negative breast cancer is a high-risk breast cancer with poor survival rate. To date, there is a lack of targeted therapy for this type of cancer. One unique phenomenon is that inflammatory breast cancer is frequently triple negative. However, it is still ambiguous how inflammation influences triple-negative breast cancer growth and responding to chemotherapy. Herein, we investigated the levels of inflammation-associated enzyme, iNOS, in 20 triple-negative breast cancer patients’ tumors, and examined its correlation with patients’ responses to platinum-based neoadjuvant chemotherapy. Our studies showed that triple-negative breast cancer patients with attenuated iNOS levels in tumor cells after treatment showed better responses to platinum-based neoadjuvant chemotherapy than other triple-negative breast cancer patients. Our further in vitro studies confirmed that induction of proper levels of NO increased the resistance to cisplatin in triple-negative MDA-MB-231 cells. Our data suggest that aberrant high level of iNOS/NO are associated with less effectiveness of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer. Therefore, we propose to monitor iNOS levels as a new predictor for triple-negative breast cancer patient’s response to platinum-based neoadjuvant chemotherapy. Moreover, iNOS/NO is considered as a potential target for combination therapy with platinum drugs for triple-negative breast cancer.