Coptidis Rhizoma Suppresses Metastatic Behavior by Inhibiting TGF-beta-Mediated Epithelial-Mesenchymal Transition in 5-FU-Resistant HCT116 Cells

Colorectal cancer (CRC) is the second most lethal malignancy worldwide. The high mortality rate of CRC is largely due to cancer metastasis. Recently, suppressing epithelial-to-mesenchymal transition (EMT) has been considered a promising strategy for treating metastatic cancer, especially drug-resistant metastatic cancer. The present study aimed to evaluate the antimetastatic effect of Coptidis Rhizoma, as well as the potential underlying mechanisms, using a 5-fluorouracil-resistant colon tumor cell model (HCT116/R). Coptidis Rhizoma 30% ethanol extract (CRE) significantly inhibited HCT116/R cells migration and invasion. CRE effectively inhibited EMT in HCT116/R cells by upregulating the expression of an epithelial marker (E-cadherin) and downregulating the expression of mesenchymal markers (vimentin, Snail, and ZEB2) at both the protein and gene levels. Immunofluorescence assays also confirmed consistent patterns in the levels of E-cadherin and vimentin. In addition, the anti-EMT activity of CRE and its related effects were associated with the CRE-mediated suppression of the TGF-beta pathway, as shown by changes in the levels of downstream molecules (phosphorylated Akt and p38), and inhibition of migration, invasion, and protein expression of TGF-beta after treatment/cotreatment with a TGF-beta inhibitor (SB431542). In conclusion, Coptidis Rhizoma exerts an antimetastatic effect, especially in the treatment of drug-resistant cancer, and the possible mechanisms are associated with inhibiting EMT via TGF-beta signaling. Thus, Coptidis Rhizoma will likely become a potential therapeutic candidate for simultaneously mitigating drug resistance and metastasis in CRC.

Automated summary

Colorectal cancer is the second most lethal malignancy worldwide, and its high mortality rate is largely due to cancer metastasis. Suppression of epithelial-to-mesenchymal transition (EMT) has emerged as a promising strategy for treating metastatic cancer. This study evaluated the antimetastatic effect of Coptidis Rhizoma, a traditional Chinese medicine, on drug-resistant colon cancer cells and found that it inhibits EMT through the TGF-beta signaling pathway.