Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer.
Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer.
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纳米症：一种稀土纳米颗粒，是一种新型的卵巢癌抗血管生成治疗剂。
DOI：
10.1371/journal.pone.0054578
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shridhar V
中科院分区：
文献类型：
--
作者：
Giri S;Karakoti A;Graham RP;Maguire JL;Reilly CM;Seal S;Rattan R;Shridhar V
卵巢癌（OvCa）是美国妇女所有癌症死亡的第五大常见原因，也是妇科恶性肿瘤死亡的主要原因。虽然大多数OvCa患者最初对手术切除和化疗有反应，但75%的患者后来死于这种疾病。因此，迫切需要测试新的治疗药物来抵消与OvCa相关的高死亡率。在此背景下，我们开发并设计了纳米铈（NCe），即氧化铈纳米颗粒，具有抗氧化特性，用作OvCa的治疗剂。我们首次发现NCe显著抑制A2780细胞活性氧（ROS）的产生，减弱生长因子（SDF1、HB-EGF、VEGF165和HGF）介导的SKOV3细胞迁移和侵袭，而不影响细胞增殖。NCe处理还能抑制VEGF165诱导的人脐血管内皮细胞（HUVEC）增殖、毛细血管形成、VEGFR2和MMP2的激活。裸鼠腹腔注射NCe （0.1 mg/kg体重）处理A2780卵巢癌细胞后，肿瘤生长明显减少（p<0.002），肿瘤大小减小，Ki67染色明显降低肿瘤细胞增殖。通过透射电子显微镜（TEM）和电感耦合等离子体质谱（ICP-MS）分析，发现治疗组肿瘤中有NCe的积累。通过CD31染色减少和血管内皮细胞特异性凋亡观察到，肿瘤体积的减小伴随着血管新生的减弱。综上所述，这些结果表明，氧化铈基NCe是一种新型纳米颗粒，可能被用作卵巢癌的抗血管生成治疗剂。
Ovarian cancer (OvCa) is the fifth most common cause of death from all cancers among women in United Sates and the leading cause of death from gynecological malignancies. While most OvCa patients initially respond to surgical debulking and chemotherapy, 75% of patients later succumb to the disease. Thus, there is an urgent need to test novel therapeutic agents to counteract the high mortality rate associated with OvCa. In this context, we have developed and engineered Nanoceria (NCe), nanoparticles of cerium oxide, possessing anti-oxidant properties, to be used as a therapeutic agent in OvCa. We show for the first time that NCe significantly inhibited production of reactive oxygen species (ROS) in A2780 cells, attenuated growth factor (SDF1, HB-EGF, VEGF165 and HGF) mediated cell migration and invasion of SKOV3 cells, without affecting the cell proliferation. NCe treatment also inhibited VEGF165 induced proliferation, capillary tube formation, activation of VEGFR2 and MMP2 in human umbilical vascular endothelial cells (HUVEC). NCe (0.1 mg/kg body weigh) treatment of A2780 ovarian cancer cells injected intra-peritoneally in nude mice showed significant reduction (p<0.002) in tumor growth accompanied by decreased tumor cell proliferation as evident from reduced tumor size and Ki67 staining. Accumulation of NCe was found in tumors isolated from treated group using transmission electron microscopy (TEM) and inductively coupled plasma mass spectroscopy (ICP-MS). Reduction of the tumor mass was accompanied by attenuation of angiogenesis, as observed by reduced CD31 staining and specific apoptosis of vascular endothelial cells. Collectively, these results indicate that cerium oxide based NCe is a novel nanoparticle that can potentially be used as an anti-angiogenic therapeutic agent in ovarian cancer.
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影响因子：
4.8
作者：
Kroll, J;Waltenberger, J
通讯作者：
Waltenberger, J
影响因子：
3.7
作者：
Karakoti, A. S.;Kuchibhatla, Satyanarayana V. N. T.;Seal, S.
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