Assessment of neutralizing interleukin-4 effect on CD133 gene expression in colon cancer cell line

Cytokine. 2017 Sep:97:66-72. doi: 10.1016/j.cyto.2017.05.022. Epub 2017 Jun 2.


Colorectal cancer may be maintained by cancer stem-like cells (CSCs) that express the cell surface marker CD133. CSCs (CD133+cells) exhibits greater resistance to the chemotherapy and this resistance may be mediated in part by an autocrine response to IL4. The aim of the study was to assess the effect of anti-IL4 antibody alone or in combination with chemotherapy on the CD133 expression andthe tumor growth. We used Caco cell line in our experiments and the samples were as the following; untreated colorectal cell line, cells treated by chemotherapy, cells treated by anti-IL4 antibody in 3doses (2.5, 5, 10μg/ml), cells treatedby combination of chemotherapy and anti-IL4 antibody in 3 doses. Results of our in vitro studies demonstrated that anti-IL4 inhibited growth of Caco cell line in a dose-dependent manner revealing a 32.11% inhibition at the highest concentration (10µg/ml). There was further significant inhibition by combination of anti IL4 and chemotherapy in a dose response manner when compared to group treated by chemotherapy only. These effects were associated with decreased expression of CD133 in tumor cells also. Lastly, anti-IL4 antibody stimulated apoptosis. Our study suggested that neutralizing of IL4 by anti IL4 antibody affect the CD133+ cells may be by increasing their apoptosis. The effects of anti IL4 antibody either, alone or in combination with chemotherapy, inhibited the tumor growth and decreased the viable tumor cells. Furthermore, neutralizing of IL4 increased the efficacy of chemotherapy treatment.

Keywords: CD133 gene; Cancer growth; Chemotherapy; Colorectal cancer; IL4.

MeSH terms

  • AC133 Antigen / genetics*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Caco-2 Cells
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / immunology
  • Fluorouracil / pharmacology
  • Gene Expression
  • Humans
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / immunology*
  • Interleukin-4 / pharmacology*


  • AC133 Antigen
  • Antibodies, Neutralizing
  • Antineoplastic Agents
  • IL4 protein, human
  • PROM1 protein, human
  • Interleukin-4
  • Fluorouracil