Objective: To explore the function and possible mechanism of berberine on colon cancer cell SW620 based on Kirsten rat sarcoma viral oncogene homolog(KRAS) promoter G-quadruplex target

by investigating its effect on colon cancer cells proliferation and whether berberine could inhibit mRNA expression of KRAS in colon cancer cells through regulating its promoter G-quadruplex. Method: The inhibition rate of berberine on SW620 cell lines proliferation was determined by using 3-(4

5-dimethyl-2-thiazolyl)-2

5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The binding capacity of KRAS G-quadruplex DNA with berberine was detected by methods of fluorescence spectra

and the anionic quenching experiment

and fluorescence anisotropy and fluorescence polarization experiment were used to investigate their binding mode. The effect of berberine on conformation of KRAS G-quadruplex was studied by using circular dichroism spectra; the effect of berberine on thermal stability of KRAS G-quadruplex was studied by using circular dichroism spectra variable-temperature experiment

and the effect of berberine on KRAS genetic transcription of SW620 cells was detected by real-time quantitative polymerase chain reaction (Real-time PCR). Result: Berberine can inhibit the proliferation of SW620 cells in a dose dependent manner. KRAS G-quadruplex DNA had a stronger binding capacity with berberine at a stoichiometric ratio of about 1:1

with a binding constant of (0.93±0.21)×106 L·mol-1

under a binding mode of complex patterns of terminal stacking and groove binding. Berberine can keep the parallel conformation and thermostability of KRAS G-quadruplex

and 100 μmol·L-1 berberine can inhibit the mRNA expression of KRAS in SW620 cells. Conclusion: Berberine can bind with KRAS promoter G-quadruplex DNA and keep the thermostability of its parallel conformation

and may down-regulate KRAS genetic transcription of SW620 cells by affecting its G-quadruplex structure

which may be one of the mechanisms for inhibiting the proliferation of cells. KRAS promoter G-quadruplex structure may become a new target in colon cancer therapy.