Synergistic Inhibition of Colorectal Cancer Growth by Qingjie Fuzheng Granule and 5-Fluorouracil through the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway

Objective: The aim is to study the synergistic effects of Qingjie Fuzheng Granule (QFG) and 5-fluorouracil (5-FU) on colorectal cancer and elucidate its mechanism. Materials and Methods: Chou-Talalay was used to calculate the combination index of QFG and 5-FU; the synergistic anti-cancer ability of QFG and 5-FU that targets phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was studied in human colorectal cells and its xenograft mice. Results: QFG and 5-FU synergistically inhibited the growth of HCT-8 cells. QFG combined with 5-FU inhibited proliferation, migration and invasion, as well as promoted apoptosis through regulating related proteins in HCT-8 cells and in mice. Furthermore, QFG and 5-FU down-regulated 5-FU metabolism-related enzymes such as thymidylate synthase and dihydropyrimidine dehydrogenase. In addition, it blocked PI3K/AKT signaling pathway and alleviated cancer-related functions (proliferation, migration, and invasion) through this pathway. Conclusions: QFG combined with 5-FU exerts synergistic anti-cancer effects though blocking the PI3K/AKT signaling pathway.