Dysosma versipellis Extract Inhibits Esophageal Cancer Progression through the Wnt Signaling Pathway

In this study, we aim to investigate the effect of Dysosma versipellis extract on biological behavior of esophageal cancer cells and its underlying mechanisms.

A total of 30 BALB/C nude mice (class SPF) were equally and randomly divided into the control group, model group, and Dysosma versipellis group. CP-C cell of esophageal cancer was subcutaneously injected into the model group as well as the Dysosma versipellis group, and the same amount of normal saline into the control group, in order to compare the tumorigenesis of nude mice of three groups. Wnt, β-catenin, and p-GSK3β/GSK3β expression in tumor tissues was detected using Western blot. CP-C cells in logarithmic growth were selected and divided into 4 groups, including the control group, podophyllotoxin group, Wnt activator group, and combined group (mixture of podophyllotoxin and Wnt activator). The cell viability, apoptosis, and invasion ability, Wnt, β-catenin, and p-GSK3β/GSK3β expression level of CP-C cells in each group were detected via MTT assay, flow cytometry, transwell, and Western blot, respectively.

The tumorigenesis rates of the control group, model group, and Dysosma versipellis group were 0%, 90% (1 tumor-free mouse), and 80% (2 tumor-free mice), respectively. The tumor mass in the Dysosma versipellis group was significant less than that in the model group. Based on the results of Western blot, Wnt, ß-catenin, and p-GSK3β/GSK3β expression of the Dysosma versipellis group was lower than that of the control group. The in vitro viability test indicated that there was a significant difference in cell viability exhibited among four groups. Cell viability level in the 3 groups, including the combined group, blank group, and Wnt activator group, was higher than the podophyllotoxin group at each time point. In vitro apoptosis assay revealed that significant differences in cell apoptosis exhibited among four groups. Cell apoptosis rate was higher in the podophyllotoxin group compared to the remaining three groups. The Wnt activator group showed the lowest cell apoptosis rate. The in vitro invasion assay demonstrated that numbers of transmembrane cell in the 3 groups, involving the combined group, blank group, and Wnt activator group, showed a higher level than the podophyllotoxin group. The results of Western blot manifested that the podophyllotoxin group showed lower level of Wnt, ß-catenin, and p-GSK3β/GSK3β expression compared to the other 3 groups.

Podophyllotoxin in Dysosma versipellis has an excellent antiesophageal cancer effect and is able to inhibit cell viability as well as invasion ability and promote apoptosis of esophageal cancer cells by inhibiting the Wnt signaling pathway, which could be potentially used in future clinical treatment of esophageal cancer.