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利格列汀-环丙沙星联合用药对宫颈癌细胞系的协同细胞毒性作用:对靶向热休克蛋白60的见解

Synergistic Cytotoxic Impact of Linagliptin - Ciprofloxacin Combination on Cervical Cancer Cell Line: Insights into Targeting Heat Shock Protein 60.

作者信息

Al-Mahdawi Tiba Th, Said Ali Muafaq, Hade Istikrar M, Yasin Youssef Shakuri, Jumaa Azal Hamoody

机构信息

Bilad Alrafidain University, College of Pharmacy, Diyala, Iraq.

Al-Amarah University College, Amarah, Iraq.

出版信息

Asian Pac J Cancer Prev. 2025 Jun 1;26(6):2117-2128. doi: 10.31557/APJCP.2025.26.6.2117.

Abstract

OBJECTIVE

This study aimed to assess the combined impact of linagliptin and ciprofloxacin on inhibiting cervical cancer cell line proliferation and their ability to target heat shock protein 60.

METHODS

The anticancer properties of the linagliptin-ciprofloxacin combination were assessed employing the HeLa cervical cancer cell line, with incubation periods of 24 and 72 hours. The human fibroblast cell line (HFF) was utilized to evaluate the mixture's safety. The concentrations of linagliptin, ciprofloxacin, and their combination varied between 0.1 and 1000 µg/ml. combination index value was estimated to assess the potential synergistic impact of linagliptin and ciprofloxacin. The study also employs computational molecular docking simulations to evaluate the affinity of linagliptin and ciprofloxacin for binding to heat shock protein 60.

RESULTS

The study's findings demonstrated that the combination of linagliptin and ciprofloxacin markedly inhibited the proliferation of cervical cancer cells. The inhibitory effect depended on the concentration of the mixture and the incubation duration. It concurrently exhibits a diminished impact on the viability of the HFF cell line. The combination index study indicates that the interaction between linagliptin and ciprofloxacin shows a synergistic effect across all concentrations, particularly after 24 hours of incubation. The computational molecular docking simulation demonstrated that linagliptin and ciprofloxacin can bind with Hsp 60. The docking scores for linagliptin and ciprofloxacin were recorded at -7.6 kcal/mol and -8.1 kcal/mol, respectively.

CONCLUSION

Our study findings from the MTT assay, combination index, and computational docking simulations indicate that the combination of linagliptin and ciprofloxacin presents a promising option for treating cervical cancer, considering their defined adverse effects and pharmacokinetic profiles.

摘要

目的

本研究旨在评估利那格列汀与环丙沙星联合使用对抑制宫颈癌细胞系增殖的综合影响及其靶向热休克蛋白60的能力。

方法

采用HeLa宫颈癌细胞系评估利那格列汀 - 环丙沙星组合的抗癌特性,孵育时间为24小时和72小时。用人成纤维细胞系(HFF)评估该混合物的安全性。利那格列汀、环丙沙星及其组合的浓度在0.1至1000μg/ml之间变化。估计组合指数值以评估利那格列汀和环丙沙星的潜在协同作用。该研究还采用计算分子对接模拟来评估利那格列汀和环丙沙星与热休克蛋白60结合的亲和力。

结果

研究结果表明利那格列汀与环丙沙星的组合显著抑制宫颈癌细胞的增殖。抑制作用取决于混合物的浓度和孵育持续时间。它同时对HFF细胞系的活力影响较小。组合指数研究表明,利那格列汀和环丙沙星之间的相互作用在所有浓度下均显示出协同作用,尤其是在孵育24小时后。计算分子对接模拟表明利那格列汀和环丙沙星可以与Hsp 60结合。利那格列汀和环丙沙星的对接分数分别记录为 -7.6 kcal/mol和 -8.1 kcal/mol。

结论

我们从MTT试验、组合指数和计算对接模拟得出的研究结果表明,考虑到利那格列汀和环丙沙星明确的不良反应和药代动力学特征,它们的组合是治疗宫颈癌的一个有前景的选择。

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