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Ara-C increases gastric cancer cell invasion by upregulating CD-147-MMP-2/MMP‑9 via the ERK signaling pathway
Guang-Lin Yang1, Hai-Rong Tao2, Han-Wei Wang3
1Department of General Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
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.
Insights
Low-dose Ara-C increases gastric cancer cell invasion by upregulating CD-147, MMP-2, and MMP-9 via the ERK pathway. This finding helps prevent chemotherapy side effects.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Gastric cancer cells show limited sensitivity to Ara-C, a DNA synthesis inhibitor.
- Understanding Ara-C's effects on gastric cancer cell proliferation and invasion is crucial.
Purpose of the Study:
- To investigate the role of Ara-C in gastric cancer cell proliferation, apoptosis, and invasion.
- To elucidate the molecular mechanisms underlying Ara-C's effects on gastric cancer cells.
Main Methods:
- Cell Counting Kit-8 for proliferation assessment.
- Gelatin zymography for MMP-2 and MMP-9 activity.
- RT-PCR and Western blotting for gene and protein expression analysis (CD-147, MMP-2, MMP-9).
- In vitro invasion assays with and without U-0126 or siRNA-CD147.
Main Results:
- Low-dose Ara-C did not significantly affect cell proliferation but increased invasion.
- Ara-C upregulated MMP-2, MMP-9, CD-147 expression, and ERK activation.
- U-0126 and siRNA-CD147 treatments inhibited Ara-C-induced invasion.
Conclusions:
- Ara-C enhances gastric cancer cell invasiveness through CD-147/MMP-2/MMP-9 expression via the ERK signaling pathway.
- Findings offer insights for preventing Ara-C-related collateral damage in chemotherapy.
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