Abstract
Background
The interaction between platelets and tumor cells is a crucial step in the progression of tumor metastasis. Blocking platelet-tumor cells interaction is a potential target against metastasis. Ginsenoside Rb (G-Rb) exhibits potential anti-tumor pharmacological properties and may offer a therapeutic option for cancer.
Purpose
This study aimed to investigated anti-metastatic effects of G-Rb through regulating the crosstalk of platelets with tumor cells.
Methods
In order to explore anti-metastatic effects of G-Rb in vitro, HepG2 cell and platelets were co-cultured to mimic the interaction of platelets with tumor cells. Wound healing and Transwell assays were used to assess the effect of G-Rb on cell migration and invasion. The expression of epithelial-mesenchymal transition (EMT) related markers was determined by RT-qPCR and western blot assays. The aggregation and activation of platelets were detected by flow cytometry. Moreover, a lung metastasis model of mice was established to evaluate inhibitory effects of G-Rb in vivo. Metastatic nodules on the lung surface were counted and Sections of lung tissues were stained by H&E.
Results
G-Rb effectively suppressed tumor metastasis in the co-culture of platelets with HepG2 cell. First, G-Rb treatment significantly inhibited the migration and invasion of HepG2 cells induced by platelets. Second, the expressions of EMT-related markers, including N-cadherin, Snail and MMP9, were decreased by the treatment of G-Rb in the presence of platelets. Meanwhile, G-Rb also suppressed platelets hyperactivity by regulating the adhesion to tumor cells, activation, TCIPA and TGF-β1 secretion of platelets in vitro. In addition, the results of in vivo experiments proved G-Rb administration not only significantly decreased lung metastasis but also attenuated platelets aberrant aggregation and activation in vivo.
Conclusion
Our findings showed that G-Rb inhibited tumor metastasis and platelet activation through mediating platelets-tumor cells interaction, indicating the potential values of G-Rb in tumor metastasis therapy.