A recent study reported that
plumbagin downregulated the activity of
Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway to show various antitumor effects in
multiple myeloma cells. We aimed in this in vitro study to demonstrate the inhibition of JAK2/STAT3 pathway by
plumbagin through inducing SH2-containing
protein tyrosine phosphatase 1 (SHP1) expression in the MKN-28
gastric cancer cell line. We performed western blot analysis to measure SHP1, phosphor-JAK2/STAT3 level, and observed that
plumbagin induced SHP1 expression and simultaneously downregulated phosphor-JAK2/STAT3 in MKN-28 cells, with negative SHP1 expression. This effect was consistent when JAK2/STAT3 signaling was activated by
interleukin-6 (IL-6), and ameliorated when cells were treated with prevanadate, a
protein tyrosin
phosphatase inhibitor. Furthermore,
plumbagin significantly reduced gene expression of
cyclin D1,
vascular endothelial growth factor (VEGF)-1, Bcl-xL,
survivin and
matrix metalloproteinase-9 (MMP-9), known target products of STAT3 activation in gastric
carcinogenesis by reverse transcription-polymerase chain reaction (RT-PCR). Several functional studies such as water soluble tetrazolium salt-1 (WST-1) assay,
wound closure assay,
Matrigel invasion assay and
Annexin V assay were also performed, and we validated the functional effect of
plumbagin for inhibition of cell proliferation, migration and invasion, and induction of apoptosis. Collectively, our findings suggest that
plumbagin is a potential regulator of cellular growth, migration, invasion and apoptosis by inhibiting both constitutive and inducible STAT3 activity through induction of SHP1 in
gastric cancer cells.