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


CONCLUSIONS
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.
Liang
Yong-Ju
YJ
Cancer Center,Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Fu
Li-Wu
LW
Ding
Yan
Y
Xiong
Hui-Yu
HY
Chen
Li-Ming
LM
Yang
Xiao-Ping
XP
Pan
Qi-Chao
QC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000473:pathology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D005047:Etoposide; C028098:10-hydroxycamptothecin; D002166:Camptothecin