Combination of angiogenesis inhibitor TNP-470 with cytotoxic drugs in experimental therapy of nasopharyngeal carcinoma.
This study was conducted to evaluate the effectiveness of angiogenesis inhibitor 6-O-(N-chloroacetyl-carbamoyl)-fumagillol (TNP-470. AGM-1470) in the treatment of nasopharyngeal carcinoma (NPC) alone and in combination with cytotoxic agents. Forty-two male BALB/c nude mice bearing human NPC cell line CNE-2 were randomized into 6 groups: those treated with saline solution, TNP-470, cisplatin (DDP), fluorouracil (5-FU), TNP-470 + DDP, and TNP-470 + 5-FU, respectively. In every treatment group, tumor growth was suppressed significantly. The combination of 5-FU with TNP-470 showed significant enhancement in antitumor efficacy. TNP-470 also enhanced the inhibitory effect of DDP, although not to statistical significance. All animals gained in body weight, although treatment with 5-FU caused slight, reversible diarrhea of 2 to 3 days' duration. The results showed that TNP-470 suppressed the growth of the human NPC cell line and enhanced the antitumor effect of 5-FU without increasing its toxicity. The combination of angiogenesis inhibitors with conventional cytotoxic agents is promising in the treatment of NPC.
Qian
C N
CN
Department of Nasopharyngeal Carcinoma, Cancer Center, Sun Yat-sen University of Medical Sciences, Guangzhou, People's Republic of China.
Min
H Q
HQ
Lin
H L
HL
Hong
M H
MH
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D003510:Cyclohexanes; D004353:Drug Evaluation, Preclinical; D005472:Fluorouracil / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009368:Neoplasm Transplantation; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D012717:Sesquiterpenes; D002945:Cisplatin; D005472:Fluorouracil; D000077609:O-(Chloroacetylcarbamoyl)fumagillol