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熊果酸纳米颗粒通过诱导细胞凋亡在体外和体内抑制宫颈癌生长。

Ursolic acid nanoparticles inhibit cervical cancer growth in vitro and in vivo via apoptosis induction.

作者信息

Wang Shaoguang, Meng Xiaomei, Dong Yaozhong

机构信息

Department of Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.

出版信息

Int J Oncol. 2017 Apr;50(4):1330-1340. doi: 10.3892/ijo.2017.3890. Epub 2017 Feb 22.

Abstract

Cervical cancer is a cause of cancer death, making it one of the most common causes of death among women globally. Previously, a variety of studies have revealed the molecular mechanisms by which cervical cancer develops. However, there are still limitations in treatment for cervical cancer. Ursolic acid is a naturally derived pentacyclic triterpene acid, exhibiting broad anticancer effects. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions. Administration of ursolic acid nanoparticles is thought to be sufficient to lead to considerable suppression of cervical cancer progression. We loaded gold-ursolic acid into poly(DL-lactide-co-glycolide) nanoparticles to cervical cancer cell lines due to the properties of ursolic acid in altering cellular processes and the easier absorbance of nanoparticles. In addition, in this study, ursolic acid nanoparticles were administered to cervical cancer cells to find effective treatments for cervical cancer inhibition. In the present study, ELISA, western blotting, flow cytometry and immunohistochemistry assays were carried out to calculate the molecular mechanism by which ursolic acid nanoparticles modulated cervical cancer progression. Data indicated that ursolic acid nanoparticles, indeed, significantly suppress cervial cancer cell proliferation, invasion and migration compared to the control group, and apoptosis was induced by ursolic acid nanoparticles in cervical cancer cells through activating caspases, p53 and suppressing anti-apoptosis-related signals. Furthermore, tumor size was reduced by treatment of ursolic acid nanoparticles in in vivo experiments. In conclusion, this study suggests that ursolic acid nanoparticles inhibited cervical cancer cell proliferation via apoptosis induction, which could be a potential target for future therapeutic strategy clinically.

摘要

宫颈癌是癌症死亡的一个原因,使其成为全球女性中最常见的死亡原因之一。此前,各种研究已经揭示了宫颈癌发生发展的分子机制。然而,宫颈癌的治疗仍然存在局限性。熊果酸是一种天然衍生的五环三萜酸,具有广泛的抗癌作用。已知纳米颗粒药物递送系统与仅使用药物溶液相比,在鼻内给药时能提高药物的生物利用度。熊果酸纳米颗粒的给药被认为足以显著抑制宫颈癌的进展。由于熊果酸在改变细胞过程中的特性以及纳米颗粒更容易被吸收,我们将金-熊果酸负载到聚(DL-丙交酯-共-乙交酯)纳米颗粒中用于宫颈癌细胞系。此外,在本研究中,将熊果酸纳米颗粒施用于宫颈癌细胞以寻找抑制宫颈癌的有效治疗方法。在本研究中,进行了酶联免疫吸附测定(ELISA)、蛋白质印迹法、流式细胞术和免疫组织化学分析,以计算熊果酸纳米颗粒调节宫颈癌进展的分子机制。数据表明,与对照组相比,熊果酸纳米颗粒确实能显著抑制宫颈癌细胞的增殖、侵袭和迁移,并且熊果酸纳米颗粒通过激活半胱天冬酶、p53并抑制抗凋亡相关信号,诱导宫颈癌细胞凋亡。此外,在体内实验中,熊果酸纳米颗粒治疗可减小肿瘤大小。总之,本研究表明熊果酸纳米颗粒通过诱导凋亡抑制宫颈癌细胞增殖,这可能是未来临床治疗策略的一个潜在靶点。

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