Background/Objectives: Soft tissue sarcomas are rare, heterogeneous tumors with limited therapeutic options and suboptimal outcomes in advanced stages. Lurbinectedin is a promising new antineoplastic alkylating agent. This study investigates its cytotoxic effects and its potential as a radiosensitizing agent on soft tissue sarcoma. Methods: Four soft tissue sarcoma cell lines were treated with lurbinectedin alone or in combination with ionizing radiation. Single-dose irradiation in a 4-day protocol was compared with prolonged treatment and an additional fractionated ionizing radiation scheme in a 6-day protocol. Cellular responses were analyzed by flow cytometry for apoptosis (Annexin V)/necrosis (7AAD) and cell cycle (Hoechst), clonogenic cell survival, and scratch assays for cell migration. Results: In the 4-day protocol, lurbinectedin induced G2/M arrest in all cell lines (p= 0.029) and significantly increased apoptosis/necrosis (p= 0.029) in SW-872. Lurbinectedin-treatment resulted in a decrease (p≤ 0.002) of clonogenic cells in all cell lines. In the scratch assay, cell migration was delayed in two cell lines (p= 0.048) after lurbinectedin-treatment. Additional radiotherapy had no significant effect compared to lurbinectedin-monotherapy in apoptosis/necrosis and G/2M arrest in the 4-day protocol, clonogenic cell assay, and scratch assay. In the 6-day protocol, lurbinectedin induced an increase (p= 0.029) in G2/M arrest in all cell lines and apoptosis/necrosis in three cell lines, while resulting in a decrease (p< 0.001) of clonogenic cells. Additional radiotherapy had a significant effect on the decrease in clonogenic cells (p≤ 0.048) in two cell lines but did not increase G2/M arrest and apoptosis/necrosis. Conclusions: Lurbinectedin had strong effects on three of the selected cell lines by inducing G2/M arrest, promoting apoptosis/necrosis, and reducing clonogenic survival, suggesting that it may be a promising chemotherapeutic agent in soft tissue sarcoma treatment. The effect on the fourth cell line was limited, as well as the effect on cell migration. Single-dose irradiation occasionally interfered with the effects of Lurbinectedin, whereas adding fractionated irradiation caused an additional decrease in clonogenic survival, indicating that the combination of Lurbinectedin with fractionated ionizing radiation may have promising effects.
背景/目的：软组织肉瘤是一种罕见且异质性的肿瘤，在晚期阶段治疗选择有限且疗效欠佳。Lurbinectedin是一种前景广阔的新型抗肿瘤烷化剂。本研究探讨其对软组织肉瘤的细胞毒性作用及其作为放射增敏剂的潜力。方法：采用Lurbinectedin单药或联合电离辐射处理四种软组织肉瘤细胞系。通过4天方案的单次照射与延长治疗及6天方案中额外分次电离辐射方案进行比较。通过流式细胞术检测细胞凋亡（膜联蛋白V）/坏死（7AAD）和细胞周期（Hoechst染色），采用克隆形成细胞存活实验和划痕实验分析细胞迁移能力。结果：在4天方案中，Lurbinectedin在所有细胞系中诱导G2/M期阻滞（p=0.029），并在SW-872细胞系中显著增加细胞凋亡/坏死（p=0.029）。Lurbinectedin处理使所有细胞系的克隆形成细胞数量减少（p≤0.002）。划痕实验中，两个细胞系在Lurbinectedin处理后细胞迁移延迟（p=0.048）。在4天方案的细胞凋亡/坏死、G2/M期阻滞、克隆形成实验及划痕实验中，联合放疗与Lurbinectedin单药治疗相比未产生显著差异。在6天方案中，Lurbinectedin在所有细胞系中诱导G2/M期阻滞增加（p=0.029），在三个细胞系中促进细胞凋亡/坏死，同时导致克隆形成细胞数量减少（p<0.001）。联合放疗对两个细胞系克隆形成细胞的减少具有显著影响（p≤0.048），但未增强G2/M期阻滞和细胞凋亡/坏死。结论：Lurbinectedin通过诱导G2/M期阻滞、促进细胞凋亡/坏死及降低克隆形成存活率，对三种选定细胞系产生显著作用，提示其可能成为软组织肉瘤治疗中具有潜力的化疗药物。其对第四种细胞系的作用有限，对细胞迁移的影响亦不显著。单次照射偶尔会干扰Lurbinectedin的效应，而联合分次照射可进一步降低克隆形成存活率，表明Lurbinectedin与分次电离辐射联合治疗可能具有良好前景。
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