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

Abstract

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.

miR-29b negatively regulates MMP2 to impact gastric cancer development by suppress gastric cancer cell migration and tumor growth

“…The 3'UTR of human MMP2 mRNA is 1264 bp in length and contained a complementary site for the seed region of miR-29b (Figure 1 B). In addition in a previous study, MMP2 had been shown to be up-regulated in gastric cancer 5 , 25 , suggesting that miR-29b may regulate gastric cancer development by targeting MMP2.…”

“…As one of the most common malignant tumors, early diagnosis and treatment for GC has become an urgent issue. Studies have shown that a series of complicated process such as Helicobacter pylori infection 4 , cell proliferation and cell cycle dysfunction 5 , angiogenesis 6 , 7 , cell invasion and metastasis 8 cross-talked and promoted the development of GC. Multiple molecular alterations such as oncogenes and tumor suppressor genes were involved in the development of GC 9 .…”

Quercetin Inhibits the Migration and Invasion of HCCLM3 Cells by Suppressing the Expression of p-Akt1, Matrix Metalloproteinase (MMP) MMP-2, and MMP-9

“…MMP-2/MMP-9 are members of the matrix metalloproteinase (MMP) family, and both proteins are implicated in tumor migration, invasion, and metastasis in various cancers, like cervical cancer [ 3 ], prostate cancer [ 4 ], and gastric cancer [ 5 , 6 ]. Moreover, metastasis is inhibited when MMP-2/MMP-9 are down-regulated in the SK HEP 1 and MHcc97H HCC cell lines [ 7 ].…”

miR-15a-3p and miR-16-1-3p Negatively Regulate Twist1 to Repress Gastric Cancer Cell Invasion and Metastasis

“…Because of the high mortality of GC, early diagnosis and treatment has become an urgent issue. Previous studies indicated that the occurrence and development of GC is a complicated process that involves a variety of cross-linked factors such as environmental infection 5, cell proliferation and cell cycle dysfunction 6, angiogenesis 7, 8, cell invasion and metastasis9. Molecular mechanism studies showed that GC involves aberrant expression of oncogenes, tumor suppressor genes, apoptosis-related genes and metastasis-related genes 4.…”