The Effects of Ginsenoside Compound K on PDGF-BB-Induced PASMCs Proliferation and Phenotypic Conversion of Pulmonary Arterial Smooth Muscle Cells

  Objective   To explore the inhibitory effects of ginsenoside compound K (CK) on pulmonary arterial smooth muscle cells (PASMCs) proliferation and phenotypic conversion in vitro and investigate its related mechanisms.

  Methods   PASMCs cultured in vitro were examined in the study. They were induced with platelet-derived growth factor-BB (PDGF-BB) and then treated with CK. The cells were randomly assigned to the control group (receiving no treatment), the model group (PDGF-BB, 20 ng/mL), and the intervention group (20 ng/mL PDGF-BB+5 μmol/L CK). The cell proliferation was measured by CCK-8 assay (on the basis of the above group assignment, concentrations of CK was set at 1, 3, and 5 μmol/L in the intervention group, and the drug group was added, receiving 1, 3, and 5 μmol/L CK, respectively). Cell cycle and apoptosis were examined by flow cytometry. The levels of mRNA and proteins of α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α), markers of phenotypic conversion, were detected by quantitative real-time PCR and Western blot. The levels of protein expression related to Wnt/β-catenin signaling pathway were examined by Western blot.

  Results   Compared with the model group, CK significantly inhibited PDGF-BB-induced proliferation of PASMCs in a dose-dependent way. The results of 5 μmol/L CK intervention were not significantly different from that of the control group (P>0.05). Hence, 5 μmol/L CK was chosen for subsequent experiments. Separate treatment of PASMCs with CK at doses of 1, 3, and 5 μmol/L did not reveal any cytotoxicity to PASMCs (P>0.05). CK also arrested the cell cycle of PASMCs at the G₀/G₁ phase, promoted the apoptosis of PASMCs, and reversed the mRNA and protein expression of α-SMA and SM22α (P<0.01). In addition, CK down-regulated the expressions of cyclin D1 and β-catenin, while it up-regulated the protein expressions of phosphorylated glycogen synthase kinase-3β (pGSK-3β)/glycogen synthase kinase-3β (GSK-3β) (P<0.01).

  Conclusion   CK was capable of inhibiting the abnormal proliferation of PASMCs and reversing the phenotypic conversion, and its acting mechanism may be related to the Wnt/β-catenin signaling pathway, suggesting the therapeutic potential of CK in controlling pulmonary arterial hypertension.