Corilagin enhances the anti-tumor activity of 5-FU by downregulating the expression of GRP 78

Abstract

Colorectal cancer is one of the most common malignancies worldwide. Although initially effective, patients who receive chemotherapy ultimately experience various complications and develop chemo-resistance, leading to cancer recurrence. Therefore, we aimed to find a drug with good efficacy and low toxicity that could enhance the treatment with 5-Fluorouracil (a commonly used clinical drug) and reduce its dosing. Corilagin, an anti-tumor natural product, has received widespread attention. Glucose regulated protein 78 (GRP78) is overexpressed in colorectal cancer cells and plays a key role in the proliferation, migration and drug resistance of cancer cells. Importantly, GRP78 can affect the apoptosis induced by 5-fluorouracil in CRC cells. In the present study, we determined the synergistic anti-tumor activity of the combination treatment by cell proliferation assay, apoptosis assay, fluorescent staining, cell cycle analysis, WB and PCR assays. This synergistic effect was associated with S-phase blockade, intracellular reactive oxygen species production and downregulation of GRP78. Taken together, our results indicate that Corilagin acts as a potentiator of 5-fluorouracil and may have therapeutic potential for patients with CRC.