title: ECRG2enhances the anti-cancer effects of cisplatin in cisplatin-resistant esophageal cancer cellsviaupregulation ofp53and downregulation ofPCNA.
abstract: OBJECTIVE
  To explore the anti-tumor effects of esophageal cancer-related gene 2 (ECRG2) in combination with cisplatin (DDP) in DDP-resistant esophageal cancer cells (EC9706/DDP).
  
  
  METHODS
  A drug-resistant cell model was established, with EC9706/DDP cells being treated with ECRG2 and/or DDP. Cell viability was examined by MTT assay. The rate of cell apoptosis was determined by flow cytometry. The mRNA expression levels of proliferating cell nuclear antigen (PCNA), metallothionein (MT), and p53 were determined by RT-PCR and PCNA, while MT and p53 protein expression levels were determined by western blotting.
  
  
  RESULTS
  The anti-proliferative effect of ECRG2 in combination with DDP was superior when compared to ECRG2 or DDP alone. The inhibition rate for the combination reached its peak (51.33%) at 96 h. The early apoptotic rates of the control, ECRG2 alone, DDP alone, and ECRG2 plus DDP groups were 5.71% ± 0.27%, 12.68% ± 0.61%, 14.15% ± 0.87%, and 27.96% ± 0.36%, respectively. Although all treatment groups were significantly different from the control group (P< 0.05), the combination treatment of ECRG2 plus DDP performed significantly better when compared to either ECRG2 or DDP alone (P< 0.05). The combination of ECRG2 and DDP significantly upregulated p53 mRNA and protein levels and downregulated PCNA mRNA and protein levels compared to ECRG2 or DDP alone (P< 0.05). However, no changes were seen in the expression of MT mRNA or protein.
  
  
  CONCLUSIONS
  ECRG2in combination with DDP can inhibit viability and induce apoptosis in esophageal cancer DDP-resistant cells, possiblyviaupregulation ofp53expression and downregulation ofPCNAexpression. These findings suggest that the combination of ECRG2 and DDP may be a promising strategy for the clinical treatment of esophageal cancers that are resistant to DDP.
authors.affiliation: Xin-Fang Hou, Shuai Li, Chen Wu, Ju-Feng Wang, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China.
authors.forename: Xin-Fang
authors.initials: XF
authors.lastname: Hou
authors.affiliation: Xin-Fang Hou, Shuai Li, Chen Wu, Ju-Feng Wang, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China.
authors.forename: Lin-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Xin-Fang Hou, Shuai Li, Chen Wu, Ju-Feng Wang, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Song
authors.affiliation: Xin-Fang Hou, Shuai Li, Chen Wu, Ju-Feng Wang, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Xin-Fang Hou, Shuai Li, Chen Wu, Ju-Feng Wang, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.affiliation: Xin-Fang Hou, Shuai Li, Chen Wu, Ju-Feng Wang, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China.
authors.forename: Ju-Feng
authors.initials: JF
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004359:Drug Therapy, Combination; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D005434:Flow Cytometry; D006801:Humans; D008668:Metallothionein / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D000074162:Serine Peptidase Inhibitors, Kazal Type; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D018809:Proliferating Cell Nuclear Antigen; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; D011994:Recombinant Proteins; C473799:SPINK7 protein, human; D000074162:Serine Peptidase Inhibitors, Kazal Type; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D008668:Metallothionein; D002945:Cisplatin
keywords: Cisplatin; Esophageal cancer related-gene 2; Proliferating cell nuclear antigen; Resistance; p53