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基于二氧化硅的纳米粒子合成及其对人前列腺癌细胞增殖的抑制作用。

Synthesis of Silica Based Nanoparticles Against the Proliferation of Human Prostate Cancer.

机构信息

Department of Biochemistry, Science Faculty, Selcuk University, Konya, Turkey.

Chemistry and Chemical Processing Technology Department, Technical Sciences Vocational School, Konya Technical University, Konya, Turkey.

出版信息

Anticancer Agents Med Chem. 2021;21(18):2553-2562. doi: 10.2174/1871520621666210208105521.

Abstract

BACKGROUND

Prostate cancer (PCa) has the second-highest morbidity and mortality rates in men. Possessing facile surface chemistry and unique optical properties make silica nanoparticles(SiO-NPs) promising cancer therapy materials.

OBJECTIVE

This study aimed to investigate the effects of SiO-NPs and their derivatives, including SiNP-NH2, SiNP-Cl, and SiNP-SH against PCa and clarify their molecular mechanism on cell death, gene, and protein expressions.

METHODS

Following the synthesis and derivation of SiO-NPs, their characterization was carried out using TEM, DLS, BET, and FT-IR. Cytotoxic properties of the compounds were investigated against different human cancerous cells; including HUH-7, A549, DLD-1, HeLa, NCI-H295R, and PC-3, as well as human healthy epithelium cell line PNT1A.

RESULTS

SiNP-NH2, SiNP-Cl, and SiNP-SH dose-dependently inhibited the proliferation of PC-3 cells with an IC value as 55.46 μg/mL, 55.09 μg/mL and 72.89 μg/mL, respectively. SiNP-SH significantly(p<0.0001) inhibited metastasis and invasion of PC-3 cells(20.4% and 46.7%, respectively), and significantly(p<0.0001) increased early apoptosis(32.3%) when compared with non-treated cells. Protein and mRNA expressions of BcL-2, Bax, caspase-3, caspase-9, caspase-12, p53, Smad-4, Kras, and Nf-ĸB were also altered following the treatment of SiO-NPs and its derivatives.

CONCLUSION

Our results demonstrated that -SH functioned SiO2-NPs can prevent the proliferation of human PCa by increasing apoptosis by up-regulating gene and protein expression of p53(TP53) as well as caspase-3, caspase-9, and caspase-12 in the apoptotic pathway. Besides, the increased level of Smad-4 has also implicated the decreased cell proliferation. Hence, low sized SiNP-SH nanoparticles might be a suitable candidate for the treatment of human PCa.

摘要

背景

前列腺癌(PCa)是男性发病率和死亡率第二高的疾病。二氧化硅纳米粒子(SiO-NPs)具有易于修饰的表面化学性质和独特的光学特性,使其成为有前途的癌症治疗材料。

目的

本研究旨在探讨 SiO-NPs 及其衍生物(包括 SiNP-NH2、SiNP-Cl 和 SiNP-SH)对前列腺癌的影响,并阐明其在细胞死亡、基因和蛋白表达方面的分子机制。

方法

在合成和衍生 SiO-NPs 后,使用 TEM、DLS、BET 和 FT-IR 对其进行了表征。研究了这些化合物对不同人类癌细胞(包括 HUH-7、A549、DLD-1、HeLa、NCI-H295R 和 PC-3 以及人健康上皮细胞系 PNT1A)的细胞毒性。

结果

SiNP-NH2、SiNP-Cl 和 SiNP-SH 呈剂量依赖性地抑制 PC-3 细胞的增殖,IC 值分别为 55.46μg/mL、55.09μg/mL 和 72.89μg/mL。SiNP-SH 显著(p<0.0001)抑制了 PC-3 细胞的转移和侵袭(分别为 20.4%和 46.7%),与未处理的细胞相比,早期凋亡显著增加(32.3%)。SiO-NPs 及其衍生物处理后,BcL-2、Bax、caspase-3、caspase-9、caspase-12、p53、Smad-4、Kras 和 NF-κB 的蛋白和 mRNA 表达也发生了改变。

结论

我们的研究结果表明,-SH 功能化的 SiO2-NPs 通过上调凋亡途径中 p53(TP53)以及 caspase-3、caspase-9 和 caspase-12 的基因和蛋白表达,增加细胞凋亡,从而抑制人前列腺癌的增殖。此外,Smad-4 水平的升高也暗示了细胞增殖的减少。因此,小尺寸的 SiNP-SH 纳米粒子可能是治疗人类前列腺癌的合适候选物。

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