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

Yang,Guang-Lin; Tao,Hai-Rong; Wang,Han-Wei; Sun,Yun; Zhang,Li-Di; Zhang,Chao; He,Wei; Xu,Mang-Hua; Zhao,Jiang-Min; Gao,Feng-Hou

doi:10.3892/or.2015.3748

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

Authors:
- Guang-Lin Yang
- Hai-Rong Tao
- Han-Wei Wang
- Yun Sun
- Li-Di Zhang
- Chao Zhang
- Wei He
- Mang-Hua Xu
- Jiang-Min Zhao
- Feng-Hou Gao
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Affiliations: Department of General Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China, Department of Orthopaedic Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China, Department of Hematology and Rheumatology, Bengbu Third People's Hospital Affiliated to Southeast University, Bengbu, Anhui 233000, P.R. China, Department of Clinical Laboratory, Dong-Nan Hospital, Shanghai 200023, P.R. China, Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China, Department of Radiology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
Published online on: January 23, 2015 https://doi.org/10.3892/or.2015.3748
Pages: 2045-2051

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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 proliferation 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.

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