抄録
Cancer is the most common cause of death and colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. Previous studies have shown that Antrodia cinnamomea (AC) can prevent or treat poisoning, diarrhea, hypertension and various types of cancer. Therefore, we purified another antroquinonol derived, AC009, to investigate the anti-tumor effects of this AC extract on CRC cells. By using cell viability assay, we found that AC009 antroquinonol derivative reduced the viability of several human CRC cell lines, including DLD-1, RKO, HCT116, and SW480. Moreover, AC009 treatment resulted in a decrease in DNA synthesis, G0/G1 phase arrest, and apoptosis. Furthermore, we found that AC009-induced cells apoptosis was caspase-dependent. In addition, AC009 treatment reduced the protein levels of phospho-Erk1/2, phospho-JNK1/2/3, and Bcl-2 showing that AC009-induced apoptosis may be via MAPK pathway. Moreover, we demonstrated that AC009 could significantly inhibit in vivo tumor growth in xenograft mice models. By using mRNA and miRNA microarray, we found the KRAS gene expression was also regulated by miRNA specific target gene. AC009 also suppresses cancer stem cell marker CD22+/CD44+ and re-sensitized the tumor inhibition effect of cetuximab in KRAS mutant colorectal cancer. We found that miRNA 27a also have the ability to re-sensitized re-sensitized the tumor inhibition effect of cetuximab in KRAS mutant colorectal cancer KRAS mutant colorectal cancer, and these effects may mediated by miRNA 27a. Taken together, our results suggest that AC009 have the therapeutic potential against human CRC cells.
