Expression of Inhibitor of Differentiation-1 and Its Effects on Angiogenesis in Gastric Cancer

Cancer Biother Radiopharm. 2016 Sep;31(7):233-7. doi: 10.1089/cbr.2016.2043.

Abstract

Objective: To explore the effects of recombinant human endostatin (endostar, ES) and cisplatin on the growth of gastric cancer-transplanted tumor in nude mice and the expression of microvessel density (MVD).

Methods: Human gastric cancer SGC-7901 cells were subcutaneously injected into the armpit of nude mice to prepare cancer-bearing nude mice. A total of 32 cancer-bearing nude mice were divided into four groups (each group with 8 mice). The four groups included control group and other three groups in which mice were treated with 5 mg/kg of ES (group E), 5 mg/kg of cisplatin (group Ci), and 5 mg/kg of ES combined with 5 mg/kg of cisplatin (group C), respectively. MVD was determined by immunohistochemistry, and the expressions of mRNA and protein of inhibitor of differentiation-1 (ID1) and vascular endothelial growth factor (VEGF) were detected with reverse transcription polymerase chain reaction (RT-PCR) and western blot, respectively. Apoptosis was observed with transmission electron microscope.

Results: Compared with control group, the sizes and weights of tumors were significantly decreased in other three groups (all p < 0.05). MVD was significantly lower in groups E, Ci, and C than in control group, and in groups E and C than in group Ci (all p < 0.05). Compared with control group, the expressions of mRNA and protein of ID1 and VEGF significantly decreased in groups E and C (all p < 0.05). There were no significant differences in the expressions of mRNA and protein of ID1 and VEGF between group Ci and control group. There was apoptosis in groups E and C, but no apoptosis was found in group Ci and control group.

Conclusion: ES can inhibit the growth of gastric cancer cells through suppressing angiogenesis and promoting apoptosis of tumor cell. This study provides a new idea for the treatment of gastric cancer.

Keywords: cisplatin; gastric cancer; inhibitor of differentiation-1; recombinant human endostatin.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology
  • Endostatins / administration & dosage
  • Endostatins / pharmacology
  • Heterografts
  • Humans
  • Inhibitor of Differentiation Protein 1 / biosynthesis*
  • Inhibitor of Differentiation Protein 1 / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microvessels / drug effects
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Random Allocation
  • Recombinant Proteins / pharmacology
  • Stomach Neoplasms / blood supply*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism

Substances

  • Endostatins
  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • RNA, Messenger
  • Recombinant Proteins
  • endostar protein
  • Cisplatin