Schelz Zsuzsanna, Muddather Hiba F, Jaski Fatemeh Sheihaki, Bózsity Noémi, Zupkó István
Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
Curr Issues Mol Biol. 2024 Jun 27;46(7):6566-6579. doi: 10.3390/cimb46070391.
Cervical cancer presents a significant challenge to the global health of women. Despite substantial advances in human papillomavirus (HPV)-related cervical cancer vaccines, non-HPV-related cervical cancer is still waiting novel therapeutic options. Drug repurposing has provided a promising approach to improve cancer therapy in recent years. Our study aimed to explore the potential in vitro antineoplastic effects of levosimendan on cervical cancer cells. The antiproliferative effects of levosimendan were investigated on cervical cancer cells using a standard MTT assay. Fluorescent double staining was performed to identify its ability to induce apoptosis and necrosis. The possible mechanism of action of levosimendan was explored using cell-cycle analysis. Furthermore, antimetastatic effects were investigated using a wound-healing assay and a Boyden chamber assay. Our results revealed that levosimendan exhibited the highest growth-inhibitory effect in the HPV-negative C33A cell line. However, the effects were modest compared to the standard agent, cisplatin. Cell-cycle analysis detected that levosimendan can induce cell-cycle arrest in C33A cells by increasing the G1 and G2/M phases, decreasing the S phase, and enhancing the hypodiploid subG1 population. Levosimendan inhibited cell migration and invasion in a concentration-dependent manner. As levosimendan showed antimetastatic efficacy, it could be considered for repurposing to contribute to overcoming resistance to therapy in cervical cancer.
宫颈癌对全球女性健康构成重大挑战。尽管人乳头瘤病毒（HPV）相关宫颈癌疫苗取得了重大进展，但非HPV相关宫颈癌仍在等待新的治疗选择。近年来，药物重新定位为改善癌症治疗提供了一种有前景的方法。我们的研究旨在探索左西孟旦对宫颈癌细胞的体外抗肿瘤作用潜力。使用标准MTT法研究左西孟旦对宫颈癌细胞的抗增殖作用。进行荧光双重染色以确定其诱导凋亡和坏死的能力。使用细胞周期分析探索左西孟旦可能的作用机制。此外，使用伤口愈合试验和博伊登小室试验研究抗转移作用。我们的结果显示，左西孟旦在HPV阴性的C33A细胞系中表现出最高的生长抑制作用。然而，与标准药物顺铂相比，其作用较为温和。细胞周期分析检测到左西孟旦可通过增加G1期和G2/M期、减少S期以及增加亚G1期低二倍体细胞群，诱导C33A细胞的细胞周期停滞。左西孟旦以浓度依赖的方式抑制细胞迁移和侵袭。由于左西孟旦显示出抗转移疗效，可考虑将其重新定位用于克服宫颈癌治疗耐药性。
