Investigating the synergistic effects of Peiminine in combination with 5-FU on the expression profile of miR-181 and miR-106 genes in colorectal cancer cells.

Abstract

Introduction:

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Emerging evidence highlights the critical role of microRNAs (miRNAs) in regulating cancer progression, therapeutic response, and drug resistance. Peiminine, a bioactive alkaloid derived from traditional Chinese medicine, has demonstrated anticancer potential in various cancer types. This study aims to investigate the synergistic effects of Peiminine in combination with 5-Fluorouracil (5-FU) on the expression profiles of miR-181 and miR-106 in colorectal cancer cells.

Material & method:

Colorectal cancer cell lines (HT-29) were treated with Peiminine, 5-FU (1 and 0.5 μg/ml), and their combination at optimized concentrations (1,5,10,50,100,150,200 and 400 ug/ml). Cell viability was assessed using MTT to evaluate the combined cytotoxic effects. Quantitative real-time PCR (qRT-PCR) was performed to determine the expression levels of miR-181 and miR-106 following each treatment. Flow cytometry was used to examine programmed cell death (apoptosis). Statistical significance was determined using ANOVA and post hoc tests.

Results:

The IC50 value of 5-FU was calculated as 2.902 µg/mL at 24 hours, while Peiminine as a single treatment exhibited an IC50 of 0.431 µg/mL at 24 hours. In the combined treatment, the IC50 of Peiminine at 24 hours was determined to be 359.4 µg/mL and 78.42 µg/mL when combined with 0.5 µg/mL and 1 µg/mL of 5-FU, respectively. The combination of 5-FU and Peiminine in HT-29 cells increased the relative expression of the miR-181 gene at the RNA level, although this increase was not statistically significant. In contrast, the relative expression of the miR-106 gene at the RNA level was significantly reduced (p < 0.005). Furthermore, the combination treatment induced apoptosis in 92% of HT-29 cells.

Conclusion:

Peiminine enhances the anticancer efficacy of 5-FU in colorectal cancer cells by modulating the expression of miR-181 and miR-106. The observed synergistic interaction presents a promising therapeutic approach to improve CRC treatment outcomes. Further studies are required to elucidate the underlying molecular mechanisms and validate these findings in vivo.