PEGylated Titanium Dioxide Nanoparticle-bound Doxorubicin and Paclitaxel Drugs Affect Prostate Cancer Cells and Alter the Expression of DUSP Family Genes.

IF 3 4区医学 Q3 CHEMISTRY, MEDICINAL Anti-cancer agents in medicinal chemistry Pub Date : 2025-01-01 DOI:10.2174/0118715206330115241015092548

Zuhal Tuncbilek, Nese Keklikcioglu Cakmak, Ayca Tas, Durmus Ayan, Yavuz Silig

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Abstract

Background: Prostate cancer (PC) is among the cancer types with high incidence and mortality. New and effective strategies are being sought for the treatment of deadly cancers, such as PC. In this context, the use of nanocarrier systems containing titanium dioxide (TiO₂) can improve treatment outcomes and increase the effectiveness of anticancer drugs.

Objective: This study aimed to evaluate the cytotoxic activity of doxorubicin (DOX) and paclitaxel (PTX) drugs on the PC cell line by attaching them to PEGylated TiO₂ nanoparticles and to examine their effect on the expression levels of dual-specificity phosphatase (DUSP) genes.

Methods: Free DOX and PTX drugs, DOX and PTX compounds bound to the pegylated TiO₂ system were applied to DU-145 cells, a PC cell line, under in vitro conditions, and MTT analysis was performed. Additionally, the IC₅₀ values of these compounds were analyzed. In addition, the expression levels of DUSP1, DUSP2, DUSP4, DUSP6, and DUSP10 genes were measured using RT-PCR. Additionally, bioinformatics and molecular docking analyses were performed on DUSP proteins.

Results: The cytotoxic activity of PTX compound bound to PEGylated TiO₂ was found to be higher than that of DOX compound bound to PEGylated TiO₂. Additionally, when the expression levels were compared to the control group, the expression levels of DUSPs were found to be lower in the drugs of the drug carrier systems.

Conclusion: Accordingly, it was predicted that the PEGylated TiO₂ nano-based carrier could be effective in PC.

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聚乙二醇化二氧化钛纳米粒子结合的多柔比星和紫杉醇药物影响前列腺癌细胞并改变 DUSP 家族基因的表达。

背景：PC 是发病率和死亡率都很高的癌症类型之一。人们正在寻求新的有效策略来治疗致命的癌症，如 PC。在这种情况下，使用含有二氧化钛的纳米载体系统可以改善治疗效果，提高抗癌药物的有效性：本研究旨在评估多柔比星（DOX）和紫杉醇（PTX）药物附着在聚合二氧化钛纳米颗粒上对前列腺癌（PC）细胞系的细胞毒活性，以及它们对双特异性磷酸酶（DUSP）基因表达水平的影响：方法：在体外条件下，将游离的 DOX 和 PTX 药物、与聚合二氧化钛系统结合的 DOX 和 PTX 复合物应用于 PC 细胞系 DU-145 细胞，并进行 MTT 分析。此外，还分析了这些化合物的 IC50 值。此外，还利用 RT-PCR 技术测定了 DUSP1、DUSP2、DUSP4、DUSP6 和 DUSP10 基因的表达水平。此外，还对 DUSP 蛋白进行了生物信息学和分子对接分析：结果：发现与 PEG 化 TiO2 结合的 PTX 化合物的细胞毒性活性高于与 PEG 化 TiO2 结合的 DOX 化合物。此外，与对照组相比，药物载体系统药物中 DUSPs 的表达水平较低：因此，可以预测基于纳米二氧化钛的聚乙二醇化载体对 PC 有效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL

CiteScore

5.10

自引率

3.60%

发文量

323

审稿时长

4-8 weeks

期刊介绍： Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.