Anti-miR182 reduces ovarian cancer burden, invasion, and metastasis: an in vivo study in orthotopic xenografts of nude mice.
Anti-miR182 reduces ovarian cancer burden, invasion, and metastasis: an in vivo study in orthotopic xenografts of nude mice.
复制标题
DOI：
10.1158/1535-7163.mct-13-0982
复制
发表时间：
2014-07
影响因子：
5.7
通讯作者：
Wei JJ
中科院分区：
文献类型：
--
作者：
Xu X;Ayub B;Liu Z;Serna VA;Qiang W;Liu Y;Hernando E;Zabludoff S;Kurita T;Kong B;Wei JJ
高级别浆液性卵巢癌（HGSOC）是一种致命的疾病，其严重的后果主要是由于在诊断时广泛转移。目前的化疗减轻了肿瘤负担，但它们不能为癌症患者提供长期的益处。这些肿瘤的侵袭性生长和转移行为特征需要新的治疗选择，如抗microrna治疗，这是一种潜在的癌症治疗方式。miR-182过表达有助于侵袭性卵巢癌，主要是通过其对参与肿瘤生长、侵袭、转移和DNA不稳定的多种肿瘤抑制基因的负调控。在这项研究中，我们利用动物原位模型，利用卵巢癌细胞SKOV3（鞘内异种移植）和OVCAR3 （IP注射）模拟人类卵巢癌，研究了抗mir -182的治疗潜力。这些模型为卵巢癌的体内治疗研究提供了一个有价值的模型系统。通过影像学、组织学和分子分析的结合，我们发现在两种模型中，与对照组相比，anti-miR-182治疗可以显著降低肿瘤负荷（大小）、局部侵袭和远处转移。anti-miR-182治疗的基础主要是通过恢复miR-182靶点的表达，包括但不限于BRCA1、FOXO3a、HMGA2和MTSS1。总之，我们的研究结果强烈表明anti-miR-182可以作为治疗HGSOC的潜在治疗方式。
High-grade serous ovarian carcinoma (HGSOC) is a fatal disease, and its grave outcome is largely due to widespread metastasis at the time of diagnosis. Current chemotherapies reduce tumor burden, but they do not provide long term benefits for cancer patients. The aggressive tumor growth and metastatic behavior characteristic of these tumors demand novel treatment options such as anti-microRNA treatment which is emerging as a potential modality for cancer therapy. MicroRNA-182 miR-182 overexpression contributes to aggressive ovarian cancer, largely by its negative regulation of multiple tumor suppressor genes involved in tumor growth, invasion, metastasis, and DNA instability. In this study, we examined the therapeutic potential of anti-miR-182 utilizing the animal orthotopic model to mimic human ovarian cancer using ovarian cancer cells SKOV3 (intrabursal xenografts) and OVCAR3 (IP injection). These models provide a valuable model system for the investigation of ovarian cancer therapy in vivo. Through a combination of imaging, histological, and molecular analyses, we found that anti-miR-182 treatment can significantly reduce tumor burden (size), local invasion, and distant metastasis compared to its control in both models. The bases of anti-miR-182 treatment are mainly through the restoration of miR-182 target expression, including but not limited to BRCA1, FOXO3a, HMGA2 and MTSS1. Overall, our results strongly suggest that anti-miR-182 can potentially be used as a therapeutic modality in treating HGSOC.