Overexpression of microRNA-15 increases the chemosensitivity of colon cancer cells to 5-fluorouracil and oxaliplatin by inhibiting the nuclear factor-κB signalling pathway and inducing apoptosis

摘要

Overcoming chemoresistance is a challenge in clinical treatment. It has been reported that microRNAs (miRNAs) are involved in regulating chemosensitivity. Therefore, the present study aimed to identify the effect and mechanism of miR-15 on colon cancer chemotherapy. Reverse transcription-quantitative polymerase chain reaction was performed to measure miR-15 level sin62-paired colon cancer and para-cancerous colon tissues. The overexpression of miR-15 in HCT116 cells was induced by transfection. The effect of miR-15 on the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU) and Oxaliplatin (OX) was determined using a luminescent cell viability assay. Flow cytometry, dual-luciferase assay and western blot analysis were used to determine the potential mechanism of miR-15. The results suggested that the expression of miR-15 was decreased in tumour tissues and that overexpression of miR-15 increased the chemosensitivity of colon cancer cells to 5-Fu and OX. miR-15 promoted apoptosis in colon cancer cells treated with 5-Fu and OX by inhibiting the expression of p50, which repressed the expression of B cell lymphoma-2 and B cell lymphoma-extra large; two direct target genes of nuclear factor-κB with anti-apoptotic functions. Thus, the current study demonstrated that miR-15 increased the chemosensitivity of colon cancer cells to 5-FU and OX by inhibiting the NF-κB signalling pathway and inducing apoptosis.