Abstract: Objective To investigate the effects of honokiol on proliferation and apoptosis of human adipose-derived mesenchymal stem cells(hADSCs), and to investigate the effect of the drug on the tumor microenvironment. Methods hADSCs were incubated with different concentrations of honokiol, the proliferation of hADSCs was detected by MTS and Trypan blue staining, and cell apoptosis was assessed by annexin V/PI double staining. In the meantime, expression of mRNA and protein related to cell proliferation and apoptosis were detected by qPCR and Western blot, respectively. The expression of total MEK, phosphorylated MEK, total ERK and phosphorylated ERK proteins in the MEK-ERK1/2 signaling pathway were detected by Western blot. Results The effect of honokiol on inhibiting proliferation and promoting apoptosis of hADSCs was significantly enhanced with the increase of concentration. The expressions of proliferation-related genes CCND1, MKI67 and PCNA were down-regulated. The expressions of pro-apoptotic genes BAX and TP53 was up-regulated, and the expressions of anti-apoptotic gene BCL2 was down-regulated. Honokiol inhibited MEK and ERK1/2 phosphorylation in a concentration-dependent manner. Conclusions Honokiol inhibits proliferation and promotes apoptosis of hADSCs, and the specific mechanism is potentially related to the inhibition of MEK-ERK1/2 pathway.

Key words: honokiol, human adipose-derived mesenchymal stem cells, cell proliferation, cell apoptosis, MEK-ERK1/2