Effect of LY293111 in combination with gemcitabine in colonic cancer.
New adjuvant therapies are needed for the treatment of stage III colon cancer. The essential fatty acids, linoleic and arachidonic acid enhance tumorigenesis through the cyclooxygenase and lipoxygenase pathways. Leukotriene B4 (LTB4) is a product of 5-lipoxygenase (5-LOX) which has tumor-promoting effects. The LTB4 receptor antagonist, LY293111 inhibited tumor growth and induced apoptosis in vitro. The effectiveness of LY293111, alone and in combination with gemcitabine was investigated in a heterotopic xenograft model in athymic mice using HT29 and LoVo human colonic cancer cells. The combined therapy markedly inhibited tumor growth and could warrant consideration as a new therapeutic option.
Hennig
Rene
R
Department of Surgery and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Tarry Building, 4-711, 303 East Chicago Ave, Chicago, IL 60611, USA.
Ding
Xian-Zhong
XZ
Tong
Wei-Gang
WG
Witt
Richard C
RC
Jovanovic
Borko D
BD
Adrian
Thomas E
TE
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001565:Benzoates / Q000008:administration & dosage; D001835:Body Weight / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation; D000093542:Gemcitabine
D001565:Benzoates; C094099:LY 293111; D018102:Receptors, Leukotriene B4; D003841:Deoxycytidine; D000093542:Gemcitabine