Ara-C increases gastric cancer cell invasion by upregulating CD-147-MMP-2/MMP‑9 via the ERK signaling pathway.

Gastric cancer cell are not particularly sensitive to Ara-C, a deoxycytidine analog that affects DNA synthesis. In the present study, AGS and MKN-45 gastric cancer cell lines were treated with Ara-C to determine its role in cell prolife-ration and apoptosis. The antiproliferative effect of Ara-C was assessed using the Cell Counting kit-8. Gelatinase zymography was utilized to detect the activity of MMP-2 and MMP-9, and an in vitro invasion assay was performed. Using RT-PCR, CD-147, MMP-2 and MPP-9 mRNA levels were assessed in AGS cells with various doses of Ara-C treatment. CD-147, MMP-2 and MMP-9 protein levels were analysed in Ara-C‑treated AGS and MKN-45 cells. AGS cells were treated with or without U-0126 or siRNA-CD147 and/or Ara-C for 24 h, and an in vitro invasion assay was performed. Although low-dose Ara-C had no obvious effect on cell proliferation, it upregulated the expression of MMP-2, MMP-9 and CD-147 and ERK activation. Low-dose Ara-C increased gastric cancer cell invasion. U-0126 and siRNA-CD-147 inhibited the induction of Ara-C in gastric cancer cell invasion. Therefore, Ara-C enhances the invasiveness of gastric cancer cells by expression of CD-147 /MMP-2 and MMP-9 via the ERK signaling pathway. The results are therefore useful in the prevention of Ara-C collateral damage associated with standard, conventional protocols of chemotherapy administration.