Anti-tumor effect of angiogenesis inhibitor TNP-470 and 5-FU combined therapy on human gastric cancer xenograft.
OBJECTIVE
TNP-470, an angiogenesis inhibitor, has already been used in combination with chemotherapy to enhance its antitumor activity. The mechanism of enhanced antitumor activity in combination therapy has not been clarified, however, and few studies have described the combined effect of TNP-470 and 5-fluorouracil (5-FU) on gastric cancer. The present study was conducted to investigate the effect of TNP-470 + 5-FU on gastric cancer cell line MKN-45 in vivo and in vitro.


METHODS
MKN-45 cells were subcutaneously injected into mice that were divided into 4 groups: a control group, a 5-FU treated group, a TNP-470 treated group, and a 5-FU + TNP-470 treated group. After the inoculation, the volume of subcutaneous tumors was measured. Blood and lymphatic vessels were also analyzed for the assessment of lymphangiogenesis.


RESULTS
Compared with 5-FU or TNP-470 alone, the combined effect of TNP-470 and 5-FU significantly inhibited and suppressed tumor growth in a synergistic fashion. The combined therapy significantly suppressed both angiogenesis and lymphagenesis.


CONCLUSIONS
The study suggests that the combined therapy provides an enhanced antitumor effect on human gastric cancer. The enhanced antitumor activity is explained mainly by the stronger inhibition of angiogenesis.
Nishimura
Koji
K
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kobe, Japan. kojikoji@mbm.nifty.com
Ohno
Masakazu
M
Chung-Kang
Cheng
C
Kuroda
Yoshikazu
Y
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003510:Cyclohexanes / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D005472:Fluorouracil; D000077609:O-(Chloroacetylcarbamoyl)fumagillol