title: 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.
authors.affiliation: Department of General Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Guang-Lin
authors.initials: GL
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Tao
authors.affiliation: Department of Hematology and Rheumatology, Bengbu Third People's Hospital Affiliated to Southeast University, Bengbu, Anhui 233000, P.R. China.
authors.forename: Han-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Dong-Nan Hospital, Shanghai 200023, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Li-Di
authors.initials: LD
authors.lastname: Zhang
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Mang-Hua
authors.initials: MH
authors.lastname: Xu
authors.affiliation: Department of Radiology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Jiang-Min
authors.initials: JM
authors.lastname: Zhao
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
authors.forename: Feng-Hou
authors.initials: FH
authors.lastname: Gao
mesh_terms: D051926:Basigin / Q000235:genetics*; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003561:Cytarabine / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009570:Nitriles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
chemical_list: C497886:BSG protein, human; D002070:Butadienes; D009570:Nitriles; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C113580:U 0126; D003561:Cytarabine; D051926:Basigin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9