Bufalin-loaded Pluronic-PEI nanoparticles inhibits the invasion and metastasis of colorectal cancer via miRNA-497 mediated IGF1-R-PI3K-Akt signaling pathway

HU Ming-tai; HU Qiang; YIN Pei-hao; DUAN You-rong; LIU Lin; OUYANG Chang-juan; XIE Dong-hao; CAO Lei; QIU Yan-yan; CHENG Yun-feng; WANG Xiang-dong; ZHOU Ming; ZOU Yu; LI Rong-xin

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Bufalin-loaded Pluronic-PEI nanoparticles inhibits the invasion and metastasis of colorectal cancer via miRNA-497 mediated IGF1-R-PI3K-Akt signaling pathway

更新时间：2022-08-31

- Bufalin-loaded Pluronic-PEI nanoparticles inhibits the invasion and metastasis of colorectal cancer via miRNA-497 mediated IGF1-R-PI3K-Akt signaling pathway
- Shanghai Journal of Traditional Chinese Medicine Vol. 51, Issue 10, Pages: 89-96(2017)
- 作者机构：
  
  1. 上海市徐汇区大华医院普外科,上海,200237
  2. 上海市普陀区中心医院肿瘤实验室,上海,200062
  3. 上海市肿瘤研究所,上海,200031
  4. 上海市徐汇区大华医院大中医科,上海,200237
  5. 复旦大学附属中山医院实验中心,上海,200031
- 作者简介：
- 基金信息：
- DOI：
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HU Ming-tai, HU Qiang, YIN Pei-hao, et al. Bufalin-loaded Pluronic-PEI nanoparticles inhibits the invasion and metastasis of colorectal cancer via miRNA-497 mediated IGF1-R-PI3K-Akt signaling pathway. [J]. Shanghai Journal of Traditional Chinese Medicine 51(10):89-96(2017)
DOI：

HU Ming-tai, HU Qiang, YIN Pei-hao, et al. Bufalin-loaded Pluronic-PEI nanoparticles inhibits the invasion and metastasis of colorectal cancer via miRNA-497 mediated IGF1-R-PI3K-Akt signaling pathway. [J]. Shanghai Journal of Traditional Chinese Medicine 51(10):89-96(2017) DOI：

摘要

目的：探讨载蟾毒灵Pluronic-PEI纳米微囊通过抑制miR-497介导的IGF1-R-PI3K-Akt信号通路对大肠癌Lovo细胞体外及在裸鼠体内生长的影响及其作用机制。方法：利用慢病毒miR-497转染大肠癌Lovo细胞,观察载蟾毒灵Pluronic-PEI纳米微囊对Lovo细胞体外增殖和侵袭转移能力的影响及miR-497介导的IGF1-R-PI3K-Akt信号通路相关基因和蛋白的调控作用。建立裸鼠原位移植瘤模型,8周后处死动物,观测对成瘤的影响。结果：①与对照组比较,载蟾毒灵的纳米微囊对过表达miR-497的Lovo细胞的抑制率最显著并呈时间-剂量依赖性；并使其凋亡率从(28.93±0.24)%提高至(75.20±0.29)%,明显高于相同浓度作用的Lovo细胞和Lovo NC细胞(P<0.01)；划痕实验中过表达miR-497的Lovo细胞的迁移率从(0.083±0.019)(25 nmol/L)降低到(-0.242±0.035)(400 nmol/L), 呈剂量依赖性；②Transwell结果提示载蟾毒灵纳米微囊在25 nmol/L就能够显著抑制过表达miR-497的Lovo细胞的侵袭作用；③免疫印迹分析提示载蟾毒灵的纳米微囊和LY 294002作用Lovo NC细胞和过表达miR-497的Lovo细胞,两种细胞的p-Akt Ser 473和p-Akt Thr 308蛋白表达明显下降,而pan-Akt变化不明显。④体内实验显示载蟾毒灵纳米微囊抑制瘤体转移优于蟾毒灵组。结论：载蟾毒灵Pluronic-PEI纳米微囊可以通过抑制miR-497介导的 IGF1-R-PI3K-Akt信号通路,在体外、体内都可发挥抗结肠癌侵袭和转移的作用。

Abstract

Objective:To investigate the influence and mechanism of bufalin-loaded Pluronic- polyetherimide(PEI)nanoparticles on the growth of colorectal cancer Lovo cells in vitro and vivo via miR-497 mediated IGF1-R-PI3K-Akt signaling pathway. MethodsThe colorectal adenocarcinoma Lovo cells were transfected by lentivirus miR-497. The effects of bufalin-loaded Pluronic-PEI nanoparticles on proliferation,invasion and metastasis of Lovo cells in vitro were observed,as well as the regulation on the related gene and protein in miR-497 mediated IGF1-R-PI3K-Akt signaling pathway. The orthotopic xenograft model of colorectal cancer was established in nude mice. The mice were sacrificed after 8 weeks,and the tumor formation was observed. Results:①Compared with the control group,the proliferation inhibition rate of bufalin-loaded Pluronic-PEI nanoparticles on miR-497 overexpressed Lovo cells was the most significant and was increased in a time and dose dependent manner,and the apoptosis rate of miR-497 overexpressed Lovo cells was increased from (28.93±0.24)% to (75.20±0.29)%,which was significantly higher than that of the Lovo cells and Lovo NC cells treated with the same concentration(P<0.01). In the scratch assay,the migration rate of miR-497 overexpressed Lovo cells was decreased from (0.083±0.019)(25 nmol/L)to (-0.242±0.035)(400 nmol/L)in a dose-dependent manner. ②The Transwell assay showed that bufalin-loaded Pluronic-PEI nanoparticles at concentration of 25 nmol/L could significantly inhibit the invasion of miR-497 overexpressed Lovo cells. ③Western blot showed that the protein expressions of p-Akt Ser473 and p-Akt Thr308 in Lovo NC cells and miR-497 overexpressed Lovo cells were significantly decreased after the treatment with bufalin-loaded Pluronic-PEI nanoparticles and LY294002,but there was no obvious change on the expression of pan-Akt. ④In vivo experiments,the effects of bufalin-loaded Pluronic-PEI nanoparticles on inhibiting tumor metastasis were better than those of bufalin. Conclusion:Bufalin-loaded Pluronic-PEI nanoparticles can inhibit the invasion and metastasis of colorectal cancer in vitro and vivo via miR-497 mediated IGF1-R-PI3K-Akt signaling pathway.

关键词

蟾毒灵纳米微囊miR-497IGF1-R-PI3K-Akt大肠癌

Keywords

bufalinnanoparticlesmiR-497IGF1-R-PI3K-Aktcolorectal cancer

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