Macrophage migration inhibitory factor siRNA inhibits hepatic metastases of colorectal cancer cells

Front Biosci (Landmark Ed). 2017 Mar 1;22(8):1365-1378. doi: 10.2741/4549.

Abstract

The purpose of this study was to assess the anti-tumor effects of macrophage migration inhibitory factor (MIF) siRNA on colorectal cancer in a mouse xenograft model. MIF specific siRNA (MIF siRNA) or a nonspecific control siRNA was introduced to murine colorectal cancer CT-26 cells. Mouse xenograft models of colorectal cancer were established. MIF siRNA, control siRNA or water was injected twice a week intravenously for 4 weeks. MIF siRNA inhibited the proliferation and migration, while induced apoptosis of CT-26 cells in vitro. Injection of MIF siRNA resulted in a significant decrease of serum MIF and VEGF levels, and the weight and volume of cecum-grafted tumors in vivo. In contrast, the number of apoptotic cells and caspase-3 expression were increased by MIF siRNA in cecum graft tumor tissues. Moreover, the water and fodder consumption were significantly improved by MIF siRNA treatment. Importantly, MIF siRNA reduced the hepatic metastases from colorectal cancer. Our results suggest that siRNA targeting MIF is a promising agent for the treatment of hepatic metastasis of colorectal cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • Apoptosis
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 8 / genetics
  • Caspase 8 / metabolism
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / therapy*
  • Down-Regulation
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism
  • Intramolecular Oxidoreductases / antagonists & inhibitors*
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / prevention & control*
  • Liver Neoplasms, Experimental / secondary*
  • Macrophage Migration-Inhibitory Factors / antagonists & inhibitors*
  • Macrophage Migration-Inhibitory Factors / genetics
  • Macrophage Migration-Inhibitory Factors / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • RNA, Small Interfering / genetics
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1 / genetics
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1 / metabolism

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • Macrophage Migration-Inhibitory Factors
  • RNA, Small Interfering
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • Tiam1 protein, mouse
  • invariant chain
  • Casp3 protein, mouse
  • Casp8 protein, mouse
  • Caspase 3
  • Caspase 8
  • Intramolecular Oxidoreductases
  • Mif protein, mouse