Hydrogen Sulfide Treatment Enhanced Paclitaxel's Anticancer Effect on the ID8 Murine Epithelial Ovarian Cancer Cell Line

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2025-06-13 DOI:10.1111/fcp.70029

Gökçe Sevim Öztürk Fincan, Ayşe Kübra Kibar Güzin, Atiye Seda Yar Sağlam

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引用次数: 0

Abstract

Background

Paclitaxel is a potent agent against ovarian cancer. Hydrogen sulfide (H₂S) is of particular interest in cancer treatment research. It is known that H₂S has apoptotic and antiproliferative effects.

Objectives

We aimed to examine the potential effects of H₂S donor NaHS and paclitaxel, both individually and when co-administered, on the ID8 murine epithelial ovarian cancer cell line.

Methods

We examined the effects of the co-administration of paclitaxel and NaHS on cell viability, cytotoxicity, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), apoptosis, and proliferation in the ID8 ovarian cancer cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase tests were performed to ascertain the effect of NaHS and paclitaxel on cell viability and cytotoxicity. Caspase 3/7 levels were quantified in order to detect whether apoptosis is caspase dependent. Quantitative real-time polymerase chain reaction (qPCR) method was used to ascertain relative mRNA levels of Bcl-2, Bcl-xL, Bax, and Bak genes.

Results

The viability of ID-8 cells showed a significant reduction following the co-administration of paclitaxel and NaHS, compared to the paclitaxel administration only. The results of qPCR analysis demonstrated significant alterations in the Bcl-2, Bcl-xL, Bax, Bak, Casp3, Casp8, and Casp9 genes' mRNA levels following cotreatment. In contrast to paclitaxel alone, its co-administration with NaHS resulted in increased apoptosis and decreased ROS levels. The presence of NaHS has been observed to enhance the apoptotic impact of paclitaxel by amplifying the decline in MMP.

Conclusion

These data indicate that co-administration of H₂S with paclitaxel could be useful as a potential agent in the treatment of ovarian cancer. We found that the presence of H₂S enhanced the antitumor efficacy of paclitaxel.

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硫化氢治疗增强紫杉醇对ID8小鼠上皮卵巢癌细胞系的抗癌作用

紫杉醇是一种有效的抗卵巢癌药物。硫化氢（H2S）在癌症治疗研究中特别受关注。已知H2S具有凋亡和抗增殖作用。我们旨在研究H2S供体NaHS和紫杉醇单独或共同给药对ID8小鼠上皮性卵巢癌细胞系的潜在影响。方法研究紫杉醇和NaHS联合给药对ID8卵巢癌细胞株细胞活力、细胞毒性、活性氧（ROS）水平、线粒体膜电位（MMP）、凋亡和增殖的影响。采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑和乳酸脱氢酶试验确定NaHS和紫杉醇对细胞活力和细胞毒性的影响。定量检测Caspase 3/7水平，检测细胞凋亡是否依赖于Caspase。采用实时定量聚合酶链反应（qPCR）法测定Bcl-2、Bcl-xL、Bax和Bak基因的相对mRNA水平。结果与单独给药相比，紫杉醇与NaHS联合给药后ID-8细胞活力明显降低。qPCR分析结果显示，共处理后Bcl-2、Bcl-xL、Bax、Bak、Casp3、Casp8和Casp9基因mRNA水平显著改变。与紫杉醇单独给药相比，NaHS与紫杉醇联合给药可增加细胞凋亡，降低ROS水平。已经观察到NaHS的存在通过放大MMP的下降来增强紫杉醇对细胞凋亡的影响。结论H2S与紫杉醇合用可作为卵巢癌治疗的潜在药物。我们发现H2S的存在增强了紫杉醇的抗肿瘤作用。

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

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.