ING4 enhances paclitaxel's effect on colorectal cancer growth in vitro and in vivo

Int J Clin Exp Pathol. 2015 Mar 1;8(3):2919-27. eCollection 2015.

Abstract

Inhibitor of growth 4 (ING4) is a tumor suppressor that can inhibit cell growth and induce apoptosis. ING4 expression levels show negative correlation with the clinical stage, histological grade, and lymph node metastasis of colorectal cancer. Further insights are needed to analyze the effect of adenovirus-mediated ING4 on colorectal cancer cell growth and the response to paclitaxel treatment. In this study, we found adenovirus-mediated ING4 expression reduced proliferation and enhanced apoptosis in the SW1116 cells. p-Stat3 and Ki-67 expression significantly decreased in the SW1116 cells treated with Ad-ING4, PTX, or Ad-ING4+PTX compared with those treated with PBS or Ad-GFP both in vitro and in vivo (P<0.05). In animal experiments, the mice treated with Ad-ING4, PTX, or Ad-ING4+PTX exhibited significantly inhibited growth of SW1116 xenografts compared with those treated with PBS or Ad-GFP (P<0.05) and the combination (Ad-ING4+PTX) treatment exhibited the highest inhibition. Our results highlight that Ad-ING4 significantly inhibits growth and induces apoptosis in SW1116 colorectal cancer cells and suppresses tumor growth in SW1116 xenografts by downregulating p-Stat3 and Ki-67 expression. A combination of Ad-ING4 and PTX exhibits the highest inhibition, indicating that ING4 enhances sensitivity to chemotherapy.

Keywords: Colorectal cancer; adenovirus; inhibitor of growth family; paclitaxel; signal transducers and activators of transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Blotting, Western
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Colorectal Neoplasms / pathology*
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Homeodomain Proteins / genetics*
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Paclitaxel / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Tumor Suppressor Proteins / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Homeodomain Proteins
  • ING4 protein, human
  • Tumor Suppressor Proteins
  • Paclitaxel