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ANP reduced Hedgehog signaling-mediated activation of matrix metalloproteinase-9 in gastric cancer cell line MGC-803

Highlights•The migration and invasion in ANP-treated MGC-803 cells were significantly inhibited.•The expression of MMP-9 was significantly inhibited by ANP in MGC-803 cells.•Hh signaling pathway was significantly inhibited by ANP in MGC-803 cells.•Inhibition of Hh by ANP may contribute to inhibition on MGC-803 gastric cancer cells.AbstractObjectiveGastric cancer is the most common malignant tumor. Most patients suffering from gastric cancer die of metastasis. The role of Atrial natriuretic peptide (ANP) in inhibiting and eliminating kinds of cancer cells has been reported. Aberrant activation of Hedgehog (Hh) signaling pathway contributes to initiation and progression of various malignancies. We have previously reported that the inhibitor of Hh, cyclopamine, reduces the metastatic activity of MGC-803 via inhibiting the expression of matrix metalloproteinases (MMP)-9. It remains to be further demonstrated that ANP has the suppressive effects on invasion and metastasis in gastric cancer via Hh-mediated MMP-9 production.MethodsTranswell, western blot, qRT-PCR were used after application of ANP on MGC-803 gastric cancer cells to determine the levels of cell migration and invasion, protein levels of MMP-9 and Hh, as well as mRNAs of MMP-9 and Hh, respectively.ResultsIt was demonstrated that the migration and invasion were significantly lower, MMP-9 and Hh as well as their mRNAs were lower as well, in ANP-treated MGC-803 gastric cancer cells than those in control.ConclusionsThe expression of MMP-9 induced by aberrant activation of Hh in MGC-803 was inhibited by ANP, which may contribute to the inhibition of cell migration and invasion. These results suggested the potential of ANP to be used in gastric cancer therapy as an inhibitor targetting Hh signaling pathway to inhibit the proliferation as well as invasion and metastasis of gastric cancer.

حزب ملی عوامی فعالیت ماتریکس متالوپروتئینازها - ۹ را در رده سلولی سرطان معده MGC - ۸۰۳ با واسطه سیگنال دهی خارپشت کاهش داد.

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