OBJECTIVE: To investigate the mechanism of Ginsenoside Rh2 in inhibiting the growth of NCI-N87 cells in vitro, and to explore the possibility of Ginsenoside Rh2 becoming a STAT3 inhibitor. STUDY DESIGN: The western blot method was employed to observe the effects of Ginsenoside Rh2 on the expressions of p-STAT3, p-Jak2, p-Src, p-EGFR, p-ERK1/2, and p-Akt in NCI-N87 cells. The effects of drugs on the expressions of p-Jak2 and p-STAT3 were measured after Ginsenoside Rh2 intervention and IL-6 (20 ng/mL) stimulation. Plasmids of DN-Jak2, DN-EGFR, DN-Src, and CA-STAT3 were constructed and transiently transfected to NCI-N87 cells. After being exposed to Ginsenoside Rh2 for 24 hours, the expressions of p-STAT3, p-Jak2, p-Src, and p-EGFR were measured. Flow cytometry was applied to detect the effect of Ginsenoside Rh2 on the cell cycle and apoptosis of transfected CA-STAT3 plasmid cells. RESULTS: After treatment with Ginsenoside Rh2, the expressions of p-STAT3 (Tyr705) and p-Jak2 in NCIN87 cells decreased, and the IL-induced p-Jak2 and p-STAT3 were also inhibited. The p-Jak2 expression in the transfected four groups of cells was decreased after Ginsenoside Rh2 intervention, while the p-Src and p-EGFR expressions remained the same. The transfection of CA-STAT3 plasmid could reverse the G0/G1 phase arrest and apoptosis caused by Ginsenoside Rh2 and mitigate the inhibition of p-STAT3. CONCLUSION: Ginsenoside Rh2 selectively inhibited the phosphorylation of Tyr705 site in the STAT3 molecule of NCI-N87 cells, in which the inhibition was achieved by specific downregulation of the p-Jak2 protein. © Science Printers and Publishers, Inc.