Enhanced suppression of prostate tumor growth by combining C-CAM1 gene therapy and angiogenesis inhibitor TNP-470.
We have previously shown that C-CAM1-based gene therapy effectively suppressed prostate tumor growth in nude mice xenograft models. In this study, we examined the effects of combining C-CAM1-based therapy and TNP-470, a potent angiogenesis inhibitor, on prostate cancer in a xenografted tumor model. The direct cytotoxic effects of Ad-C-CAM1 (recombinant adenovirus containing C-CAM1 cDNA) and TNP-470 on DU145 cells in vitro were determined by microculture tetrazolium assay. The in vivo antitumor effects of either agent alone were studied in a DU145 xenografted tumor model. Cells were infected with Ad-C-CAM1 or the control virus at multiplicities of infection (m.o.i.) of 5 or 10 and then inoculated onto nude mice 48 h later. TNP-470 (0, 17 or 35 mg/kg) was given 15, 17 and 19 days after inoculation. Combined treatments in vivo were carried out to determine whether there were synergistic antitumor effects. Both Ad-C-CAM1 and the control virus were minimally toxic to DU145 in vitro. There was evident dose-dependent suppression of xenografted tumor growth by either Ad-C-CAM1 or TNP-470. By the median-effect analysis, combination of the two agents generated strong synergistic antitumor effects as shown by marked tumor suppression as compared to either treatment alone. The novel strategy may have clinical implications for the treatment of prostate cancer.
Department of Urology, National Taiwan University College of Medicine, Taipei, Taiwan 100, ROC. yspu@ha.mc.ntu.edu.tw
Yeong-Shiau
YS
Pu
Kim-Anh
KA
Do
Weiping
W
Luo
Christopher J
CJ
Logothetis
Sue-Hwa
SH
Lin
D000251:Adenosine Triphosphatases / Q000235:genetics*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D015703:Antigens, CD; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D003510:Cyclohexanes; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy; D006023:Glycoproteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D012717:Sesquiterpenes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; C087701:Ceacam2 protein, mouse; D015815:Cell Adhesion Molecules; D003510:Cyclohexanes; D006023:Glycoproteins; D012717:Sesquiterpenes; D000251:Adenosine Triphosphatases; D000077609:O-(Chloroacetylcarbamoyl)fumagillol