Department of Biochemistry, Science Faculty, Selcuk University, Konya, Turkey.
Chemistry and Chemical Processing Technology Department, Technical Sciences Vocational School, Konya Technical University, Konya, Turkey.
Anticancer Agents Med Chem. 2021;21(18):2553-2562. doi: 10.2174/1871520621666210208105521.
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.
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.
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.
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.
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.
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。
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。
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。
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。
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。