Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway

Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract, and threatens the survival and health of patients with CRC. Chemotherapy remains one of the main therapeutic approaches for patients with CRC; however, drug resistance limits the long‑term use. CRC cells with multi‑drug resistance (MDR) exhibit increased survival times and metastatic potential, which may lead to the recurrence and metastasis of CRC. In addition, MDR is one of the major causes of chemotherapy failure in clinical treatment. Hedyotis diffusa Willd (HDW) has been used in the treatment of inflammation‑associated diseases and malignant tumors, including CRC. The authors previously demonstrated that HDW could reverse MDR in CRC cells; however, its underlying mechanism, particularly in MDR‑associated metastasis, remains to be elucidated. In the present study, the drug‑resistant CRC cell line HCT‑8/5‑fluorouracil (5‑FU) was used to investigate the effect of HDW on the growth and metastasis of cancer cells. Cell viability was assessed using the MTT assay. Cell adhesion potential was evaluated using adhesion experiments. Cell migration was assessed using wound healing and Transwell assays. The mRNA and protein expression levels of crucial factors in the transforming growth factor‑β (TGF‑β) signaling pathway, including TGF‑β, Mothers against decapentaplegic homolog 4 (SMAD4), neural (N)‑cadherin, and epithelial (E)‑cadherin, were analyzed using the reverse transcription‑semi‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that the HCT‑8/5‑FU cell line was more resistant to 5‑FU and thus can be used as the resistant cell model. HDW was able to inhibit the viability, and adhesive, migratory and invasion potential of the HCT‑8/5‑FU cells. In addition, HDW was able to downregulate the expression of TGF‑β, SMAD4 and N‑cadherin, and upregulate E‑cadherin, at the gene and protein level. In conclusion, the results demonstrated that HDW may suppress the metastasis of 5‑FU‑resistant CRC cells via regulation of the TGF‑β signaling pathway, which was also considered to be one of the underlying mechanisms of its anti‑CRC effect.