CTCE‐9908, a CXC chemokine receptor 4 (CXCR4) antagonist, prevents CXCR4 phosphorylation and inhibits the interaction with chemokine ligand 12 (CXCL12) and downstream signalling pathways associated with metastasis. This study evaluated the in vitro effects of CTCE‐9908 on B16 F10 melanoma cells with the use of mathematical modelling. Crystal violet staining was used to construct a mathematical model of CTCE‐9908 B16 F10 (melanoma) and RAW 264.7 (non‐cancerous macrophage) cell lines on cell viability to predict the half‐maximal inhibitory concentration (IC50). Morphological changes were assessed using transmission electron microscopy. Flow cytometry was used to assess changes in cell cycle distribution, apoptosis via caspase‐3, cell survival via extracellular signal‐regulated kinase1/2 activation, CXCR4 activation and CXCL12 expression. Mathematical modelling predicted IC50 values from 0 to 100 h. At IC50, similar cytotoxicity between the two cell lines and ultrastructural morphological changes indicative of cell death were observed. At a concentration 10 times lower than IC50, CTCE‐9908 induced inhibition of cell survival (p = 0.0133) in B16 F10 cells but did not affect caspase‐3 or cell cycle distribution in either cell line. This study predicts CTCE‐9908 IC50 values at various time points using mathematical modelling, revealing cytotoxicity in melanoma and non‐cancerous cells. CTCE‐9908 significantly inhibited melanoma cell survival at a concentration 10 times lower than the IC50 in B16 F10 cells but not RAW 264.7 cells. However, CTCE‐9908 did not affect CXCR4 phosphorylation, apoptosis,\ or cell cycle distribution in either cell line.

中文翻译：

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CTCE-9908（趋化因子受体 4 拮抗剂）对黑色素瘤细胞存活的体外影响和数学模型


CTCE-9908 是一种 CXC 趋化因子受体 4 (CXCR4) 拮抗剂，可防止 CXCR4 磷酸化并抑制与趋化因子配体 12 (CXCL12) 的相互作用以及与转移相关的下游信号通路。本研究利用数学模型评估了 CTCE-9908 对 B16 F10 黑色素瘤细胞的体外影响。使用结晶紫染色构建 CTCE-9908 B16 F10（黑色素瘤）和 RAW 264.7（非癌性巨噬细胞）细胞系对细胞活力的数学模型，以预测半数最大抑制浓度 (IC 50 ）。使用透射电子显微镜评估形态变化。使用流式细胞术评估细胞周期分布的变化、caspase-3 导致的细胞凋亡、细胞外信号调节激酶1/2 激活、CXCR4 激活和 CXCL12 表达的细胞存活。数学模型预测 IC 50值从 0 到 100 小时。在IC 50 ，观察到两种细胞系之间相似的细胞毒性和指示细胞死亡的超微结构形态变化。浓度比IC低10倍50 , CTCE-9908 诱导细胞存活的抑制（ p = 0.0133）在 B16 F10 细胞中，但不影响任一细胞系中的 caspase-3 或细胞周期分布。本研究预测 CTCE-9908 IC 50使用数学模型计算不同时间点的值，揭示黑色素瘤和非癌细胞的细胞毒性。 CTCE-9908 在比 IC 低 10 倍的浓度下显着抑制黑色素瘤细胞存活50在 B16 F10 细胞中，但不在 RAW 264.7 细胞中。然而，CTCE-9908 不影响任一细胞系中的 CXCR4 磷酸化、细胞凋亡或细胞周期分布。