[Experimental studies on treatment of nasopharyngeal carcinoma with combination regimen of hydroxycamptothecin and etoposide]

Ai Zheng. 2003 Apr;22(4):368-71.
[Article in Chinese]

Abstract

Background & objective: Many studies showed that there is complementary effect between topoisomerase I inhibitor and topoisomerase II inhibitor. Combination of them showed synergistic action. This study was designed to investigate the experimental therapeutic effect of the combination of topoisomerase I inhibitor hydroxycamptothecin (HCPT) with topoisomerase II inhibitor etoposide (VP-16) on nasopharyngeal carcinoma (NPC), the effect of the combination of HCPT with VP-16 against NPC was studied in vitro and in vivo.

Methods: Cytotoxicity of HCPT alone, VP-16 alone, and combination of HCPT and VP-16 on NPC cell strain CNE2 were measured by MTT assay. The models of nude mice xenografts were established for investigating the effect of the combination regimen against NPC in vivo.

Results: HCPT alone and VP-16 alone have potent cytotoxicity to CNE2 cells. The IC(50) values were 13.5+/-1.2 micromol/L and 13.5+/-1.0 micromol/L, respectively. The combination of HCPT with VP-16 (1:1) showed synergistic cytotoxicity to CNE2 cells in vitro (CI< 1). In vivo experiment showed that HCPT alone (1.5 mg/kg, i.p., q2d) exhibited 13.6% inhibition growth rate;VP-16 alone (10 mg/kg, i.p., q2d) exhibited 27.3% inhibition growth rate; the combination regimen exhibited 50% inhibition growth rate.

Conclusion: The combination of HCPT with VP-16 had significant synergistic effect against NPC in vitro and in vivo. These results suggested that the combination of HCPT with VP-16 is a promising regimen to treat NPC in clinic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Drug Resistance, Neoplasm
  • Etoposide / administration & dosage
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy*
  • Topoisomerase I Inhibitors
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Topoisomerase I Inhibitors
  • Etoposide
  • 10-hydroxycamptothecin
  • Camptothecin