Genc Sidika, Taghizadehghalehjoughi Ali, Yeni Yesim, Jafarizad Abbas, Hacimuftuoglu Ahmet, Nikitovic Dragana, Docea Anca Oana, Mezhuev Yaroslav, Tsatsakis Aristidis
Department of Medical Pharmacology, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik 11230, Turkey.
Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum 25240, Turkey.
Pharmaceutics. 2023 Jan 11;15(1):245. doi: 10.3390/pharmaceutics15010245.
(1) Background: Colon cancer is one of the most common cancer types, and treatment options, unfortunately, do not continually improve the survival rate of patients. With the unprecedented development of nanotechnologies, nanomedicine has become a significant direction in cancer research. Indeed, chemotherapeutics with nanoparticles (NPs) in cancer treatment is an outstanding new treatment principle. (2) Methods: Fe3O4 NPs were synthesized and characterized. Caco-2 colon cancer cells were treated during two different periods (24 and 72 h) with Fe3O4 NPs (6 μg/mL), various concentrations of 5-FU (4−16 μg/mL), and Fe3O4 NPs in combination with 5-FU (4−16 μg/mL) (Fe3O4 NPs + 5-FU). (3) Results: The MTT assay showed that treating the cells with Fe3O4 NPs + 5-FU at 16 µg/mL for 24 or 72 h decreased cell viability and increased their LDH release (p < 0.05 and p < 0.01, respectively). Furthermore, at the same treatment concentrations, total antioxidant capacity (TAC) was decreased (p < 0.05 and p < 0.01, respectively), and total oxidant status (TOS) increased (p < 0.05 and p < 0.01, respectively). Moreover, after treatment with Fe3O4-NPs + 5-FU, the IL-10 gene was downregulated and PTEN gene expression was upregulated (p < 0.05 and p < 0.01, respectively) compared with those of the control. (4) Conclusions: Fe3O4 NPs exert a synergistic cytotoxic effect with 5-FU on Caco-2 cells at concentrations below the active drug threshold levels.
(1) 背景：结肠癌是最常见的癌症类型之一，遗憾的是，治疗方案并未持续提高患者的生存率。随着纳米技术的空前发展，纳米医学已成为癌症研究的一个重要方向。事实上，在癌症治疗中使用纳米颗粒（NPs）的化疗药物是一种杰出的新治疗原则。(2) 方法：合成并表征了Fe3O4纳米颗粒。用Fe3O4纳米颗粒（6 μg/mL）、不同浓度的5-氟尿嘧啶（4−16 μg/mL）以及Fe3O4纳米颗粒与5-氟尿嘧啶（4−16 μg/mL）的组合（Fe3O4纳米颗粒 + 5-氟尿嘧啶）在两个不同时间段（24小时和72小时）处理Caco-2结肠癌细胞。(3) 结果：MTT法显示，用16 µg/mL的Fe3O4纳米颗粒 + 5-氟尿嘧啶处理细胞24小时或72小时会降低细胞活力并增加其乳酸脱氢酶释放（分别为p < 0.05和p < 0.01）。此外，在相同的处理浓度下，总抗氧化能力（TAC）降低（分别为p < 0.05和p < 0.01），总氧化状态（TOS）增加（分别为p < 0.05和p < 0.01）。而且，与对照组相比，用Fe3O4纳米颗粒 + 5-氟尿嘧啶处理后，IL-10基因下调，PTEN基因表达上调（分别为p < 0.05和p < 0.01）。(4) 结论：在低于活性药物阈值水平的浓度下，Fe3O4纳米颗粒与5-氟尿嘧啶对Caco-2细胞具有协同细胞毒性作用。
