Downregulation of chemokine (C-C motif) ligand 5 (CCL5) induced by a novel 8-hydroxyquinoline derivative (91b1) suppresses tumor invasiveness in esophageal carcinoma

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is a particularly aggressive form of cancer with high mortality. In this study, a novel 8-hydroxyquinoline derivative (91b1) was investigated for the anticancer activities in ESCC alongside the associated mechanisms. The in vitro cytotoxic effect of 91b1 were evaluated across five ESCC cell lines using MTS assay, with cisplatin serving as a comparative standard. Changes in gene expression profile were identified by cDNA microarray and further validated by qPCR and immunostaining. Additionally, protein levels of the most significantly downregulated target in archival ESCC samples was also studied. 91b1 demonstrated comparable anticancer effect with cisplatin. Notably, CCL5 was identified as the most substantially downregulated gene, with its suppression at both mRNA and protein expression in ESCC cells, exhibiting a dose-dependent manner. The recombinant human protein of CCL5 enhanced the invasion of ESCC cells using the trans-well assay. The upregulation of CCL5 protein was also detected in 50% of ESCC cell lines. CCL5 was also overexpressed in 76.9% of ESCC specimens. The overall results indicated that 91b1 could effectively induce anticancer effect on ESCC cells through downregulating CCL5 expression with suppression of tumor invasion. Overall, these findings suggest that 91b1 effectively inhibits ESCC cell proliferation and tumor invasion by downregulating CCL5 expression, highlighting its potential as a therapeutic agent for ESCC treatment. We used microarrays to identify the most regulated gene expression of KYSE 150 cells treated with compound 91b1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE273055 | GEO | 2024/07/29

REPOSITORIES: GEO