CCN1 up-regulates the expression of SCD1 via FoxO1 pathway and affects the sensitivity to fluorouracil of colonic neoplasms / 中华普通外科杂志

ABSTRACT

Objective:To investigate the effect of CCN1 on the chemosensitivity of colon cancer cells to 5-FU .Methods:Colon cancer and adjacent tissues, colon cancer cells and normal colon epithelial cells, HCT-116 and HCT-116/5/FU cells were collected, and the SCD1 mRNA expression levels were detected by RT-qPCR; HCT-116 cells were cultured and transfected with pcDNA3.1 and CCN1 expression vectors, or infected with shNC and shCCN1 lentivirus, CCK-8 assay was used to detect cell sensitivity to 5-FU, Western blot and RT-qPCR were used to detect SCD1 mRNA expression, and oil red O staining was used to detect the lipid content. Western blot was used to detect the distribution of transcription factor FoxO1 in the nucleus and cytoplasm. The effect of CCN1 and FoxO1 on the transcriptional activity of SCD1 promoter was detected by luciferase assay.Results:Compared with control group, the expression of SCD1 was up-regulated in colon cancer tissues, cell lines and HCT-116/5-FU cells (all P<0.05); overexpression of CCN1 reduced the sensitivity to 5-FU, increased intracellular lipid deposition, and up-regulated the expression of SCD1 ( P<0.05); Knockdown of CCN1 increased the sensitivity to 5-FU, reduced intracellular lipid content and down-regulate the expression level of SCD1 ( P<0.05); CCN1 can promote FoxO1 nuclear distribution, activation or inhibition of FoxO1 activity can promote or up-regulate SCD1 expression level and promoter activity ( P<0.05). Conclusion:CCN1 may up-regulate the expression of SCD1 by activating FoxO1 activity and inhibit the sensitivity of colon cancer cells to 5-FU.