Liu Xiangyang, Yu Zhonghui, Li Yun, Huang Junzi
Department of Pharmaceutics, Second Affiliated Hospital of Dalian Medical University, Dalian 116027, Liaoning, PR China.
Heliyon. 2024 Apr 1;10(7):e29100. doi: 10.1016/j.heliyon.2024.e29100. eCollection 2024 Apr 15.
C-X3-C motif chemokine ligand 1 (CX3CL1) is a transmembrane protein, and the membranal and soluble forms of CX3CL1 exhibit different functions, although both bind to the CX3CR1 chemokine receptor. The CX3CL1/CX3CR1 axis induces many cellular responses relevant to cancer, such as proliferation, migration, invasion, and apoptosis resistance. Here we attempt to elucidate whether CX3CL1/CX3CR1 is associated with paclitaxel (PTX) resistance in gastric cancer (GC). The Gene Expression Omnibus database was queried to screen for differentially expressed genes in GC cells caused by drug resistance, and CX3CL1 was selected as a candidate. CX3CL1 was overexpressed in PTX-resistant cells and tissues. CX3CL1 loss sensitized GC cells to PTX, promoted apoptosis and DNA damage, and inhibited cell proliferation, migration, and invasion. CX3CR1 reversed the ameliorative effect of CX3CL1 silencing on PTX sensitivity in GC cells. The promotion of PTX resistance by CX3CL1/CX3CR1 was inhibited by impairment of the small GTPase Ras homolog gene family member A (RhoA) pathway and . These findings indicate that the CX3CL1/CX3CR1 expedites PTX resistance through the RhoA signaling in GC cells.
C-X3-C基序趋化因子配体1（CX3CL1）是一种跨膜蛋白，尽管CX3CL1的膜结合形式和可溶性形式均与趋化因子受体CX3CR1结合，但其功能却有所不同。CX3CL1/CX3CR1轴可诱导许多与癌症相关的细胞反应，如增殖、迁移、侵袭和抗凋亡。在此，我们试图阐明CX3CL1/CX3CR1是否与胃癌（GC）中的紫杉醇（PTX）耐药相关。通过查询基因表达综合数据库筛选出耐药导致的GC细胞中差异表达的基因，CX3CL1被选为候选基因。CX3CL1在PTX耐药细胞和组织中过表达。CX3CL1缺失使GC细胞对PTX敏感，促进细胞凋亡和DNA损伤，并抑制细胞增殖、迁移和侵袭。CX3CR1可逆转CX3CL1沉默对GC细胞PTX敏感性的改善作用。小GTP酶RhoA（Ras homolog gene family member A）通路的损伤可抑制CX3CL1/CX3CR1对PTX耐药的促进作用。这些发现表明，CX3CL1/CX3CR1通过RhoA信号通路加速GC细胞的PTX耐药。
