Effects of retinoic acid on metastasis and its related proteins in gastric cancer cells in vivo and in vitro

Acta Pharmacol Sin. 2002 Sep;23(9):835-41.


Aim: To investigate the effects of all-trans retinoic acid (ATRA) on metastasis and its related proteins in human gastric cancer cells in vivo and in vitro.

Methods: Gastric cancer cells, MGC80-3 and SGC-7901, were inoculated into spleen subcapsule of nude mice, respectively. Nude mice were administered with ATRA (0.7 mg/kg, ig) every other day. Six weeks later, nude mice were sacrificed. All the tumors formed in spleen and in liver were removed. Some of them were fixed, and then embedded. Others were kept in liquid nitrogen for further use. Expression level of proteins in tumor and in cell was analyzed by Western blot. Microvessel in tumor section was shown by immunohistochemistry and adhesive ability of cell to amnion was measured by adhesion assay.

Results: When inoculated nude mice were treated with ATRA, the xenograft tumors in spleen and metastatic tumors in liver were suppressed by 50 % respectively, and inhibition of microvessel formation in xenograft and metastatic tumors was also observed obviously. Although ATRA regulated expression of nm23 and mts1/p16 proteins at different patterns in vivo and in vitro, high ratio of nm23:mts1/p16 was in association with low adhesive activity of cells. In addition, ATRA induced ICAM-1 protein expression in vivo and in vitro.

Conclusion: ATRA inhibits the growth of xenograft tumors and their metastasis to liver. This process may be associated with regulation of metastatic related proteins, including nm23, mts1/p16, and ICAM-1 in vivo and in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Disease Models, Animal
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Monomeric GTP-Binding Proteins / metabolism*
  • NM23 Nucleoside Diphosphate Kinases
  • Neoplasm Metastasis / prevention & control
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy
  • Nucleoside-Diphosphate Kinase*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Transcription Factors / metabolism*
  • Tretinoin / pharmacology*
  • Tretinoin / therapeutic use
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor p16
  • NM23 Nucleoside Diphosphate Kinases
  • Transcription Factors
  • Intercellular Adhesion Molecule-1
  • Tretinoin
  • NME1 protein, human
  • Nme1 protein, mouse
  • Nucleoside-Diphosphate Kinase
  • Monomeric GTP-Binding Proteins