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聚乙二醇化二氧化钛纳米颗粒结合的阿霉素和紫杉醇药物影响前列腺癌细胞并改变双特异性磷酸酶(DUSP)家族基因的表达。

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

作者信息

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

机构信息

Department of Chemistry and Chemical Technologies, Yildizeli Vocational School, Sivas Cumhuriyet University, Sivas, 58500, Türkiye.

Department of Chemical Engineering, Faculty of Engineering, Sivas Cumhuriyet University, Sivas, 58140, Türkiye.

出版信息

Anticancer Agents Med Chem. 2025;25(4):257-271. doi: 10.2174/0118715206330115241015092548.

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 (TiO) 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 TiO 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 TiO system were applied to DU-145 cells, a PC cell line, under conditions, and MTT analysis was performed. Additionally, the IC 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 TiO was found to be higher than that of DOX compound bound to PEGylated TiO. 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 TiO nano-based carrier could be effective in PC.

摘要

背景

前列腺癌(PC)是发病率和死亡率较高的癌症类型之一。人们正在寻找新的有效策略来治疗致命癌症,如前列腺癌。在这种情况下,使用含有二氧化钛(TiO)的纳米载体系统可以改善治疗效果并提高抗癌药物的有效性。

目的

本研究旨在通过将阿霉素(DOX)和紫杉醇(PTX)药物附着于聚乙二醇化TiO纳米颗粒上来评估它们对PC细胞系的细胞毒性活性,并研究它们对双特异性磷酸酶(DUSP)基因表达水平的影响。

方法

将游离的DOX和PTX药物、与聚乙二醇化TiO系统结合的DOX和PTX化合物在特定条件下应用于PC细胞系DU-145细胞,并进行MTT分析。此外,分析了这些化合物的IC值。另外,使用RT-PCR测量DUSP1、DUSP2、DUSP4、DUSP6和DUSP10基因的表达水平。此外,对DUSP蛋白进行了生物信息学和分子对接分析。

结果

发现与聚乙二醇化TiO结合的PTX化合物的细胞毒性活性高于与聚乙二醇化TiO结合的DOX化合物。此外,当将表达水平与对照组进行比较时,发现药物载体系统药物中的DUSPs表达水平较低。

结论

据此预测,聚乙二醇化TiO纳米基载体可能对前列腺癌有效。

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