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分析维甲酸和载维甲酸壳聚糖纳米粒的抗癌和生物活性的作用机制。

Analysis of the mechanisms underlying the anticancer and biological activity of retinoic acid and chitosan nanoparticles containing retinoic acid.

机构信息

Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, Sivas Cumhuriyet University, 58140, Sivas, Turkey.

Feinberg Faculty of Medicine, Robert H. Lurie Cancer Research Center, Northwestern University, Chicago, IL, USA.

出版信息

Med Oncol. 2024 Sep 25;41(11):251. doi: 10.1007/s12032-024-02512-4.

Abstract

Retinoic acid (RA) has been shown in earlier investigations to have anticancer properties in various cancer cells. RA's effect on breast cancer treatment remains uncertain, though. This study investigated whether RA and chitosan nanoparticles (NPs) loaded with RA could be harmful to the MCF-7 cell line. In this study, NPs with RA were used in characterization tests. Using ELISA kits, the amounts of 8-okso-2'-deoksiguanozin (8-oxo-dG), BCL-2, Bcl-2-Associated X-protein (Bax), cleaved Poly (ADP-ribose) polymerases (PARP), total oxidant and antioxidant, and cleaved caspase-3 capacities were determined. The analysis of chitosan NPs showed that their drug-release profile, encapsulation efficiency (EE), and particle size were suitable for cell culture experiment. The EE value of NPs including RA was calculated as 83.32 ± 0.04%. The IC value for RA was 2.89 ± 0.03 µg/mL, while the IC value for RA-loaded NPs was significantly lower at 2.28 ± 0.02 µg/mL. In ELISA testing, RA and chitosan NPs containing RA at a concentration of 2 µg/mL dramatically increased the concentrations of total oxidant, cleaved caspase-3. Cleaved caspase-3 levels were quantified as 614.90 ± 3.40 pg/mg protein in the control group, 826.37 ± 5.82 pg/mg protein in RA-treated cells, and 863.52 ± 4.32 pg/mg protein in RA-NP-treated cells. Interestingly, no substantial variations were observed in the levels of the anti-apoptotic protein BCL-2. Overall, studies revealed that RA and RA-NPs promoted apoptosis in MCF-7 cells by upregulating the expression of pro-apoptotic proteins Bax, cleaved caspase-3, and cleaved PARP.

摘要

维甲酸(RA)在早期的研究中已被证明在各种癌细胞中有抗癌特性。然而,RA 对乳腺癌治疗的影响仍不确定。本研究旨在探讨 RA 和负载 RA 的壳聚糖纳米颗粒(NPs)是否会对 MCF-7 细胞系造成伤害。在本研究中,使用 NPs 进行了表征测试。使用 ELISA 试剂盒,测定了 8-氧代-2'-脱氧鸟苷(8-oxo-dG)、BCL-2、Bcl-2 相关 X 蛋白(Bax)、聚(ADP-核糖)聚合酶(PARP)、总氧化剂和抗氧化剂以及半胱天冬酶-3 的活性。壳聚糖 NPs 的分析表明,其药物释放曲线、包封效率(EE)和粒径适合细胞培养实验。RA 负载 NPs 的 EE 值计算为 83.32±0.04%。RA 的 IC 值为 2.89±0.03μg/mL,而 RA 负载 NPs 的 IC 值明显较低,为 2.28±0.02μg/mL。在 ELISA 测试中,浓度为 2μg/mL 的 RA 和负载 RA 的壳聚糖 NPs 显著增加了总氧化剂、半胱天冬酶-3 的浓度。半胱天冬酶-3 的水平在对照组中为 614.90±3.40pg/mg 蛋白,在 RA 处理的细胞中为 826.37±5.82pg/mg 蛋白,在 RA-NP 处理的细胞中为 863.52±4.32pg/mg 蛋白。有趣的是,抗凋亡蛋白 BCL-2 的水平没有明显变化。总的来说,这些研究表明,RA 和 RA-NPs 通过上调促凋亡蛋白 Bax、半胱天冬酶-3 和 PARP 的表达,促进 MCF-7 细胞凋亡。

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