MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin

World J Gastroenterol. 2014 Aug 28;20(32):11347-55. doi: 10.3748/wjg.v20.i32.11347.

Abstract

Aim: To investigate the molecular mechanisms of miRNA in advanced gastric cancers (AGCs) before and after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods: A miRNA microarray containing human mature and precursor miRNA sequences was used to compare expression profiles in serum samples of 5 patients with AGC before and after CRS + HIPEC. The upregulation of miR-218 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in SGC7901 gastric cancer cells.

Results: miRNA microarray chip analysis found that the level of miR-218 expression was upregulated more than 8 fold after CRS + HIPEC. Furthermore, miR-218 increased gastric cancer cell chemosensitivity to cisplatin in vitro and inhibited gastric cell tumor growth in nude mice in vivo (0.5 vs 0.78, P < 0.05).

Conclusion: Our results indicated that targeting miR-218 may provide a strategy for blocking the development of gastric cancer and reverse the multi-drug resistance of gastric cell lines.

Keywords: Advanced gastric cancer; Cytoreductive surgery; Hyperthermic intraperitoneal chemotherapy; MicroRNA; Multi-drug resistance; miR-218.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage*
  • Cytoreduction Surgical Procedures*
  • Dose-Response Relationship, Drug
  • Female
  • Gastrectomy / methods*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyperthermia, Induced*
  • Inhibitory Concentration 50
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Perfusion
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Time Factors
  • Transfection
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • MIRN218 microRNA, human
  • MicroRNAs
  • Cisplatin