Stat3-siRNA inhibits the growth of gastric cancer in vitro and in vivo

Cell Biochem Funct. 2015 Oct;33(7):495-502. doi: 10.1002/cbf.3148. Epub 2015 Oct 20.

Abstract

Gastric cancer remains one of the most prevalent and lethal malignancies in the world. Despite new advances in treatment and diagnosis, patients with advanced gastric cancer are still difficult to cure resulting in a high mortality rate and poor prognosis. Signal transducer and activator of transcription 3 (Stat3) is observed aberrant in multiple tumours, including gastric cancer. Stat3 overexpression was confirmed performing a vital role in tumorigenesis. In the present study, we constructed a pSi-Stat3 plasmid to silence Stat3 and investigated the effect of pSi-Stat3 on cell proliferation, apoptosis and cell cycle progression in gastric cancer cell line SGC-7901 and mice xenograft model. Downstream proteins of Stat3, including Cyclin-D1, Survivin and Bcl-2, were detected as well for the underlying mechanism exploration. It showed that pSi-Stat3 can effectively silence the expression of Stat3 and inhibits the growth of gastric tumour both in vitro and in vivo significantly via cell apoptosis and cell cycle shift induction. The findings suggest that Stat3 signal pathway might be a promising therapeutic target for tumour treatment, including gastric cancer.

Keywords: Stat3; anti-tumour; apoptosis; gastric cancer; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle
  • Cell Line, Tumor
  • Cyclin D1 / metabolism
  • Female
  • Genes, bcl-2
  • Heterografts
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Small Interfering / pharmacology*
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / genetics
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Survivin

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Survivin
  • Cyclin D1