Interestingly, among these proteins, we also observed the significantly enhanced downregulation of MCM4 and PRIM1 protein expression in RKO cells treated by the berberine and Andrographis combination (Figure 5C), as well as the same alterations in MCM4 and PRIM1 proteins in tumor xenografts (Figure 5D), highlighting the relevance of DNA replication pathway-associated genes in promoting the anti-cancer efficacy of Andrographis and berberine combination in CRC. This evidence concerns the gene MCM4 and colorectal carcinoma.