Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer.
Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer.
复制标题
DOI：
10.1007/s13346-017-0377-4
复制
发表时间：
2018-04
影响因子：
5.4
通讯作者：
Panyam J
中科院分区：
文献类型：
--
作者：
Grill AE;Shahani K;Koniar B;Panyam J
姜黄素在体外显示出对HER-2阳性肿瘤细胞有希望的抑制活性，但在体内口服生物利用度差。我们的实验室以前已经开发了一种聚合物微粒制剂，用于持续递送姜黄素进行化学预防。本研究的目的是检查姜黄素负载的聚合物微粒在HER-2癌症的转基因小鼠模型Balb-neuT中的抗癌功效。每月注射微粒，并检查小鼠的肿瘤外观和生长。与接受空微粒的对照小鼠相比，在2或4周龄时开始姜黄素微粒治疗使肿瘤出现延迟2-3周。在12周时，姜黄素微粒处理的小鼠中异常（小叶增生、原位癌和浸润性癌）乳腺组织面积显著减少，CD-31染色也是如此。姜黄素治疗显著降低了乳腺VEGF水平，这可能有助于减缓肿瘤形成。然而，与盐水对照相比，空白微粒加速肿瘤发生，姜黄素治疗消除了这种作用，表明PLGA微粒增强了该模型中的肿瘤发生。PLGA微粒给药显示与较高的血浆乳酸水平和增加的NF-κB活化相关。PLGA微粒的意外副作用可能与实现体内持续姜黄素水平所需的高剂量微粒有关。可以降低姜黄素的总剂量的方法（例如，通过增加其效力或降低其清除率）可以允许开发缓释姜黄素剂型作为癌症化学预防的实用方法。
Curcumin has shown promising inhibitory activity against HER-2 positive tumor cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has previously developed a polymeric microparticle formulation for sustained delivery of curcumin for chemoprevention. The goal of this study was to examine the anticancer efficacy of curcumin loaded polymeric microparticles in a transgenic mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and mice were examined for tumor appearance and growth. Initiating curcumin microparticle treatment at 2 or 4 weeks of age delayed tumor appearance by 2–3 weeks compared to that in control mice that received empty microparticles. At twelve weeks, abnormal (lobular hyperplasia, carcinoma in situ, and invasive carcinoma) mammary tissue area was significantly decreased in curcumin microparticle-treated mice, as was CD-31 staining. Curcumin treatment decreased mammary VEGF levels significantly, which likely contributed to slower tumor formation. When compared to saline controls, however, blank microparticles accelerated tumorigenesis and curcumin treatment abrogated this effect, suggesting that PLGA microparticles enhance tumorigenesis in this model. PLGA microparticle administration was shown to be associated with higher plasma lactic acid levels and increased activation of NF-κB. The unexpected side effects of PLGA microparticles may be related to the high dose of the microparticles that was needed to achieve sustained curcumin levels in vivo. Approaches that can decrease the overall dose of curcumin (for example, by increasing its potency or reducing its clearance rate) may allow the development of sustained release curcumin dosage forms as a practical approach to cancer chemoprevention.
登录
查看更多内容
影响因子：
4.3
作者：
Draoui N;Feron O
通讯作者：
Feron O
影响因子：
45.3
作者：
Gonzalez-Angulo, Ana M.;Litton, Jennifer K.;Hortobagyi, Gabriel N.
通讯作者：
Hortobagyi, Gabriel N.
影响因子：
5.8
作者：
Baselga, Jose;Perez, Edith A.;Bell, Richard
通讯作者：
Bell, Richard
DOI：
10.1016/j.bbamcr.2006.11.004
发表时间：
2007-03-01
影响因子：
5.1
作者：
Jung, Yunjin;Xu, Wanping;Neckers, Len
通讯作者：
Neckers, Len
影响因子：
6.2
作者：
Bendell, JC;Domchek, SM;Winer, E
通讯作者：
Winer, E