Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells

Pharmaceutical Science Advances Pub Date : 2025-05-26 DOI:10.1016/j.pscia.2025.100077

Caiyu Liu , Shengmei Gao , Bo Liu , Feipeng Zhang , Yanling Mu , Fuwen Wang , Yan Li

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Abstract

The SphK1 inhibitor development is of great importance for the treatment of non-small cell lung cancer (NSCLC). In this study, CHJ01 which has been previously shown anti-tumor effects was introduced to investigate the detailed antitumor mechanism both in vitro and in vivo. CHJ01 inhibited the A549 cell proliferation, migration, and invasion significantly and showed cytotoxicity to A549. CHJ01 induced G0/G1 cell cycle arrest by increasing ceramide levels and altered the expression of TRAF2, Bcl-2, Bax and RELA. CHJ01 inhibited the TRAF2/NF-κB signaling pathway and promoted apoptosis by downregulating Bcl-2 and upregulating Bax. In vivo anti-tumor effects were investigated using a nude mouse ectopic tumor model. CHJ01 reduced the volumes and weights of xenograft tumor in nude mice. CHJ01 induced apoptosis by HE staining and immunohistochemistry assay. These results indicated that CHJ01 can be a potential candidate for the treatment of NSCLC.

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CHJ01靶向鞘氨醇激酶1在A549细胞中的抗肿瘤活性及机制研究

SphK1抑制剂的开发对非小细胞肺癌（NSCLC）的治疗具有重要意义。本研究引入已有抗肿瘤作用的CHJ01，从体内和体外两方面详细探讨其抗肿瘤机制。CHJ01显著抑制A549细胞的增殖、迁移和侵袭，对A549具有细胞毒性。CHJ01通过提高神经酰胺水平，改变TRAF2、Bcl-2、Bax和RELA的表达，诱导G0/G1细胞周期阻滞。CHJ01通过下调Bcl-2和上调Bax，抑制TRAF2/NF-κB信号通路，促进细胞凋亡。采用裸鼠异位瘤模型研究体内抗肿瘤作用。CHJ01能降低裸鼠移植瘤的体积和重量。HE染色和免疫组化实验证实CHJ01诱导细胞凋亡。这些结果表明CHJ01可能是治疗非小细胞肺癌的潜在候选者。

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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Pharmaceutical Science Advances

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