GLB prevents tumor metastasis of Lewis lung carcinoma by inhibiting tumor adhesion actions

Acta Pharmacol Sin. 2005 Jul;26(7):881-6. doi: 10.1111/j.1745-7254.2005.00125.x.

Abstract

Aim: To investigate the inhibitory effect of a new compound of GLB on tumor metastasis in vivo and analyze its actions on tumor cell adhesion to clarify its mechanism.

Methods: The effect of GLB on tumor metastasis was analyzed by Lewis lung carcinoma model. The pathological morphology of lung alveolar was evaluated by hematoxylin-eosin staining. The effect of GLB on the proliferation of human prostate cancer cell (PC-3M, with a high metastatic characteristic) was studied using the MTT method, and its actions on PC-3M cell adhesion to human umbilical vein endothelial cells (HUVEC) and laminin were analyzed in vitro.

Results: GLB (100 mg/kg/d for 28 d, ig) reduced the number of lung colonies of Lewis lung carcinoma metastasis significantly (P<0.05). Simultaneously, GLB could mitigate the damage of lung alveolar caused by metastasic tumor deposits. In vitro, GLB inhibited dramatically the adhesion of PC-3M cells to HUVEC (P< 0.01) and laminin (P<0.05), without cytotoxic or anti-proliferative action on PC-3M cells.

Conclusion: GLB has anti-tumor metastatic activity, which partly depends on its inhibition of tumor adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Lewis Lung / pathology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Endothelial Cells / physiology
  • Female
  • Humans
  • Laminin / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / physiopathology
  • Pyrans / chemistry
  • Pyrans / pharmacology*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*
  • Umbilical Veins / cytology

Substances

  • (2''S,3aR,6S,7aR)-3''-acetyl-3a,7a-dihydro-2,2,2'-2',-tetramethyl-5'-(4-bromophenyl)-spiro(spiro(1,3-dioxolo(4,5-D)-pyrane-6(7H),5'(4'H)-1',3'-dioxolo)-7(6H),2''(3''H)-(1,3,4)-oxadiazole)
  • Antineoplastic Agents
  • Laminin
  • Oxadiazoles
  • Pyrans
  • Spiro Compounds