Soluble TRAIL gene and actinomycin D synergistically suppressed multiple metastasis of TRAIL-resistant colon cancer in the liver.
Metastatic liver tumors are highly malignant and refractory to conventional therapies. TRAIL-resistant CT-26 cells underwent apoptosis in vitro in the presence of both recombinant TRAIL (rTRAIL) and a suboptimal dose of actinomycin D (ACD). Co-administration of soluble TRAIL (sTRAIL) gene and ACD suppressed the metastatic liver tumors of CT-26, significantly inducing apoptosis in the tumors, while such effects were not demonstrated in mice that received either the sTRAIL gene or ACD alone. The gene therapy of sTRAIL with a suboptimal dose of an anticancer drug is a new strategy for treatment of multiple liver metastasis.
Ishii
Michiaki
M
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Iwai
Masaki
M
Harada
Yoshinori
Y
Kishida
Tsunao
T
Asada
Hidetsugu
H
Shin-Ya
Masaharu
M
Itoh
Yoshito
Y
Imanishi
Jiro
J
Okanoue
Takeshi
T
Mazda
Osam
O
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D003609:Dactinomycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy; D010957:Plasmids; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012995:Solubility; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection
D011500:Protein Synthesis Inhibitors; D053221:TNF-Related Apoptosis-Inducing Ligand; D003609:Dactinomycin