A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer
A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer
复制标题
化学酶法合成的胆固醇-g-聚(胺-酯)介导的p53基因递送用于在前列腺癌中实现抗肿瘤功效
DOI：
10.2147/ijn.s191905
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Li, Quanshun
中科院分区：
文献类型：
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作者：
Dong, Mengmeng;Chen, Jiawen;Li, Quanshun
背景以化学酶途径合成的两亲性阳离子共聚物胆固醇-g-聚(胺-酯)，即Chol-g-PMSC-PPDL已被用作p53基因递送的载体，以人前列腺癌细胞系PC-3(p53 null)为模型来检查其抗肿瘤功效。材料和方法通过定量PCR和Western blotting测定转染效率。采用MTT法、集落形成实验和Live/Dead染色检测抗增殖作用。通过伤口愈合和Transwell迁移实验评估抗迁移效果。结果转染效率测定表明载体介导的p53基因转染可显着提高细胞内p53的表达水平。通过p53基因传递，可以检测到明显的抗增殖作用，这被阐明与线粒体依赖性凋亡途径的同时激活和细胞周期停滞在G1期有关。同时，转染p53基因后可以获得抗迁移作用。结论 Chol-g-PMSC-PPDL 介导的 p53 基因转染可能成为实现有效抗肿瘤反应的有前景的策略。
Background An amphiphilic cationic copolymer cholesterol-g-poly(amine-co-ester), namely Chol-g-PMSC-PPDL synthesized in a chemoenzymatic route has been utilized as a carrier for p53 gene delivery to check its antitumor efficacy, using human prostate cancer cell line PC-3 (p53 null) as a model. Materials and methods The transfection efficiency was measured by quantitative PCR and Western blotting assay. The anti-proliferative effect was detected using MTT method, colony formation assay and Live/Dead staining. The anti-migration effect was evaluated through wound healing and Transwell migration assays. Results The transfection efficiency assay indicated that the carrier-mediated p53 gene transfection could dramatically enhance the intracellular p53 expression level. Through p53 gene delivery, obvious anti-proliferative effect could be detected which was elucidated to be associated with the simultaneous activation of mitochondrial-dependent apoptosis pathway and cell cycle arrest at G1 phase. Meanwhile, the anti-migration effect could be obtained after p53 gene transfection. Conclusion Chol-g-PMSC-PPDL-mediated p53 gene transfection could potentially be employed as a promising strategy for achieving effective anti-tumor response.