Therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer in vivo and in vitro

Int J Clin Exp Pathol. 2013;6(3):421-30. Epub 2013 Feb 15.

Abstract

Objective: To investigate the in vivo and in vitro therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer (NSCLC).

Methods: MTT was done to measure the cell proliferation; flow cytometry to detect cell apoptosis; Transwell invasion assay to determine the invasiveness of NSCLC. In addition, HE staining, TUNEL staining and immunohistochemistry for CD34 were employed to investigate the influence of 188Re-MAG3-depreotide on the growth of NSCLC.

Results: 1) Within 2-6 days, the inhibitory effect of 188Re-MAG3-depreotide on the proliferation of A549 cells and SPC-A1 cells increased over time. 2) At 48 h after treatment with 188Re-MAG3-depreotide, the apoptosis rate of A549 cells and SPC-A1 cells was 23.1% and 22.6%, respectively. 3) After 188Re-MAG3-depreotide treatment, the number of invasive A549 cells and SPC-A1 cells was reduced by about 3 times when compared with control group. 4) The cancer in the control group presented with unlimited growth. The cancer growth continued after treatment with 188Re or MAG3-depreotide alone, while the cancer growth was markedly inhibited after 188Re-MAG3-depreotide treatment when compared with control group.

Conclusion: 188Re-MAG3-depreotide can inhibit the proliferation and invasion of A549 cells and SPC-A1 cells. Treatment with 7.4MBq 188Re-MAG3-depreotide via tail vein can significantly suppress the in vivo cancer growth and induce the apoptosis of cancer cells. These findings demonstrate that 188Re-MAG3-depreotide can induce the apoptosis of NSCLC cells and directly kill the NSCLC cells, which provide evidence for the radiotherapy of NSCLC.

Keywords: 188Re; cancer bearing nude mice; depreotide; in vitro killing effect; non-small cell lung cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Organometallic Compounds / pharmacology*
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • 188Re-MAG3-depreotide
  • Antineoplastic Agents
  • Organometallic Compounds
  • Somatostatin