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研究硫化氢供体硫氢化钠(NaHS)在SH-SY5Y细胞系中的抗增殖机制。

Investigating the antiproliferative mechanisms of NaHS, a hydrogen sulfide donor, in the SH-SY5Y cell line.

作者信息

Öztürk Ayşegül, Joha Ziad, Başgöz Neslihan, Taşkıran Ahmet Şevki

机构信息

Departments of Therapy and Rehabilitation, Vocational School of Health Services, Sivas Cumhuriyet University, Sivas, Türkiye.

Departments of Pharmacology, Faculty of Pharmacy, Sivas Cumhuriyet University, Sivas, Turkey.

出版信息

Med Oncol. 2025 May 30;42(7):225. doi: 10.1007/s12032-025-02772-8.

Abstract

Neuroblastoma, a childhood cancer, arises from neural crest cells within the sympathetic nervous system. This study investigated the anticancer effects of the exogenous hydrogen sulfide (H₂S) donor, sodium hydrogen sulfide (NaHS), on neuroblastoma cells, elucidating how it inhibits cell proliferation. The study was conducted using the SH-SY5Y cell line. The cells were exposed to various concentrations of NaHS (32, 16, 8, 4, and 2 mM) for 24 h. Cell viability was assessed using the XTT assay. ELISA was used to measure levels of the growth signal factors HER-2, EGFR, mTOR, ERK-1, and ERK-2, as well as the apoptosis marker caspase-3. In addition, apoptosis was evaluated using the Muse Annexin V & Dead Cell Assay Kit. NaHS significantly reduced cell proliferation, as demonstrated by the XTT assay (p < 0.001). NaHS treatment also decreased levels of HER-2, EGFR, ERK-1, and ERK-2 (p < 0.05 to p < 0.01), while mTOR levels remained unchanged (p > 0.05) and caspase-3 levels increased (p < 0.001). Flow cytometry confirmed that NaHS treatment significantly increased the proportion of apoptotic cells (p < 0.001). The antiproliferative effect of NaHS against neuroblastoma appears to be mediated through the suppression of certain growth signal factors and the induction of apoptosis. These findings suggest that exogenous hydrogen sulfide donors hold promise as a potential therapeutic strategy for neuroblastoma.

摘要

神经母细胞瘤是一种儿童癌症,起源于交感神经系统内的神经嵴细胞。本研究调查了外源性硫化氢(H₂S)供体硫氢化钠(NaHS)对神经母细胞瘤细胞的抗癌作用,阐明了其抑制细胞增殖的机制。该研究使用SH-SY5Y细胞系进行。将细胞暴露于不同浓度的NaHS(32、16、8、4和2 mM)中24小时。使用XTT法评估细胞活力。采用酶联免疫吸附测定(ELISA)法检测生长信号因子HER-2、表皮生长因子受体(EGFR)、雷帕霉素靶蛋白(mTOR)、细胞外信号调节激酶-1(ERK-1)和细胞外信号调节激酶-2(ERK-2)的水平,以及凋亡标志物半胱天冬酶-3的水平。此外,使用Muse膜联蛋白V和死细胞检测试剂盒评估细胞凋亡情况。XTT法检测结果表明,NaHS显著降低了细胞增殖(p < 0.001)。NaHS处理还降低了HER-2、EGFR、ERK-1和ERK-2的水平(p < 0.05至p < 0.01),而mTOR水平保持不变(p > 0.05),半胱天冬酶-3水平升高(p < 0.001)。流式细胞术证实,NaHS处理显著增加了凋亡细胞的比例(p < 0.001)。NaHS对神经母细胞瘤的抗增殖作用似乎是通过抑制某些生长信号因子和诱导细胞凋亡来介导的。这些发现表明,外源性硫化氢供体有望成为神经母细胞瘤的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c958/12125090/a8b4b100e413/12032_2025_2772_Fig1_HTML.jpg

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