Pien Tze Huang suppresses VEGF-C-mediated lymphangiogenesis in colorectal cancer

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The majority of patients are not suitable for surgery due to the presence of metastatic disease at the time of diagnosis, which has led to a high mortality rate for patients with CRC. Lymphangiogenesis, formation of new lymphatic vessels, plays an critical role in cancer progression particularly in cancer metastasis. Vascular endothelial growth factor-C (VEGF-C) has been previously demonstrated to play a pivotal role in cancer metastasis and therefore has become an attractive target for anticancer treatments. Pien Tze Huang (PZH) is a well-known traditional Chinese formula, which has exhibited significant therapeutic effects against CRC. However, the molecular mechanisms underlying its anticancer effects, particularly in regards to antimetastasis activity, still require further elucidation. In the present study, we evaluated the effects of PZH on cell migration and VEGF-C expression using various human CRC cell lines. Moreover, using a VEGF-C-stimulated human lymphatic endothelial cell (HLEC) model, we demonstrated that PZH suppresses lymphangiogenesis by attenuating cell migration and tube formation. This indicates that PZH possesses significant antimetastatic activity. Moreover, suppression of lymphangiogenesis by PZH via the downregulation of VEGF-C may be a potential molecular mechanism by which PZH inhibits metastasis in CRC.