Background: Gastric cancer (GC) is one of the most common malignant tumors in China. Most GC patients are diagnosed at an advanced stage, for that the prognosis is dismal and metastasis is common. Although there have been increasing numbers of studies indicating that Ubenimex can suppress metastasis in GC, the underlying mechanism is still unknown.
Methods: Herein, the inhibitory effect of Ubenimex on GC metastasis, in which the underlining mechanism was determined using Gene chip analysis, high content screening (HCS), transwell assays, wound healing assays and Western blot assays.
Results: The results obtained from wound healing assays and transwell assays indicated that Ubenimex, an inhibitor of CD13, suppressed the migration and invasion of MKN-28, MGC-803, BGC-823 and SGC-790 cells, by downregulating CD13 expression. In addition, the findings acquired from Gene chip analysis and HCS demonstrated that NGFI-A-binding protein 1 (NAB1) was a putative target downstream of CD13. Furthermore, the results obtained from Western blot assays showed that Ubenimex not only inhibits NAB1 expression by targeting CD13, but also inhibits GC metastasis by mitigating the activity of the MAPK signaling pathway. These findings indicated a possible mechanism via the CD13/NAB1/MAPK pathway of which activity was restrained.
Conclusion: Ubenimex exert the inhibitory effect on GC metastasis by targeting CD13, in which NAB1 expression and the activation of MAPK signaling pathway were both suppressed. This study identified a promising target for the inhibition of GC metastasis.
Keywords: gastric cancer, CD13, Ubenimex, NAB1, MAPK