Abstract
Vasculogenic mimicry (VM) is a functional microcirculation pattern formed by aggressive tumor cells and is related to the metastasis and poor prognosis of many cancer types, including hepatocellular carcinoma (HCC). Thus far, no effective drugs have been developed to target VM. In this study, patients with liver cancer exhibited reduced VM in tumor tissues after treatment with Rhizoma Paridis. Polyphyllin I (PPI), which is the main component of Rhizoma Paridis, inhibited VM formation in HCC lines and transplanted hepatocellular carcinoma cells. Molecular mechanism analysis showed that PPI impaired VM formation by blocking the PI3k-Akt-Twist1-VE-cadherin pathway. PPI also displayed dual effects on Twist1 by inhibiting the transcriptional activation of the Twist1 promoter and interfering with the ability of Twist1 to bind to the promoter of VE-cadherin, resulting in VM blocking. This study is the first to report on the clinical application of the VM inhibitor. Results may contribute to the development of novel anti-VM drugs in clinical therapeutics.
Highlights
Despite considerable advances in treatment of hepatocellular carcinoma (HCC) in recent years, the prognosis of patients with HCC remains very poor[1]
The postoperative clinic data was analyzed and it was found that the metastasis and vascular invasion rate of HCC patients treated with Rhizoma Paridis was lower than that of patients untreated with Rhizoma Paridis (Table S6)
The results showed that patients with HCC treated with Rhizoma Paridis extract before surgery exhibited less microvessel density (MVD) and vasculogenic mimicry (VM) than the untreated patients (Fig. 1a, b)
Summary
Despite considerable advances in treatment of hepatocellular carcinoma (HCC) in recent years, the prognosis of patients with HCC remains very poor[1]. Angiogenesis is crucial to promote the growth and metastasis of HCC, which is a vascularized tumor[2]. CD34 or CD31 and periodic acid–Schiff (PAS) dualstaining have been applied to distinguish the matrix-rich morphological pattern of VM among endothelial cells undergoing angiogenesis[3]. VM has been found in several cancer types, including melanoma[3,6,7], ovarian carcinoma[8], colorectal cancer[9,10], laryngeal squamous cell carcinoma[11,12], and HCC5. VM could be related to the poor prognosis of patients with HCC13,14.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
