CX-3543 Promotes Cell Apoptosis through Downregulation of CCAT1 in Colon Cancer Cells

Abstract EN

Aim.

Colon cancer-associated transcript-1 (CCAT1), located in the vicinity of transcription factor c-Myc, was first identified in colon cancer.

A small-molecule compound CX3543 (Quarfloxin) selectively targeting Myc G-quadruplexes has entered phase II clinical trials for neuroendocrine carcinomas.

The aim of the study was to explore the relationship between CX3543, CCAT1, and cell apoptosis in colon cancer cells.

Methods.

Semiquantitative PCR was used to detect the relative expression of CCAT1 in colon cancer (CC) tissues and HT29 cell lines.

Real-time PCR (RT-PCR) was also used to investigate the expression of CCAT1 and c-Myc after HT29 cells being treated by CX3543 for 24 h.

Cell apoptosis assay and cell proliferation assay were conducted in HT29 cells after being treated by CX3543.

Results.

The results showed that the expression of CCAT1 was remarkably increased in CC tissues and HT29 cells compared to controls.

CX3543 treatment reduced the expression of c-Myc and CCAT1 and promoted cell apoptosis and inhibited cell proliferation.

After the expression of CCAT1 was inhibited by sh-CCAT1 transfection, the cell apoptosis rate was higher than that of control group.

After the cells were treated by CCAT1 overexpression plasmid transfection and CX3543, the cell apoptosis rate was lower than that of control group.

In vivo results showed that CX3543 inhibited the xenograft tumor growth of rats through downregulation of CCAT1.

Conclusion.

Our study demonstrated that CX3543 could inhibit the progression of colon cancer by downregulating CCAT1 expression and might be a potential drug for the treatment of colon cancer.