Combinatory cytotoxic effects produced by E1B-55kDa-deleted adenoviruses and chemotherapeutic agents are dependent on the agents in esophageal carcinoma.
We examined possible combinatory antitumor effects of replication-competent type 5 adenoviruses (Ad) lacking E1B-55kDa molecules (Ad-delE1B55) and chemotherapeutic agents in nine human esophageal carcinoma cells. Ad-delE1B55 produced cytotoxic effects on all the carcinoma cells and the cytotoxicity is not directly linked with the p53 status of the tumors or with the infectivity to respective tumors. A combinatory treatment with Ad-delE1B55 and an anticancer agent, 5-fluorouracil (5-FU), mitomycin C or etoposide, produced greater cytotoxic effects than that with either the Ad or the agent. Administration of 5-FU could minimally inhibit the viral replication and a simultaneous treatment with the Ad and 5-FU achieved better cytotoxicity than sequential treatments. We also confirmed the antitumor effects by the combination of Ad-delE1B55 with 5-FU in vivo. Cisplatin, however, did not achieve the combinatory effects in most of the cells tested. These data indicate that the Ad-delE1B55 produce combinatory antitumor effects with a chemotherapeutic agent irrespective of the administration schedule, but the effects depend on an agent in esophageal carcinoma.
Ma
G
G
Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.
Kawamura
K
K
Li
Q
Q
Okamoto
S
S
Suzuki
N
N
Kobayashi
H
H
Liang
M
M
Tada
Y
Y
Tatsumi
K
K
Hiroshima
K
K
Shimada
H
H
Tagawa
M
M
D000256:Adenoviridae / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D017501:Adenovirus E1B Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000494:pharmacology; D050130:Oncolytic Virotherapy; D014779:Virus Replication
D017501:Adenovirus E1B Proteins; D000970:Antineoplastic Agents; D016685:Mitomycin; D005047:Etoposide; D002945:Cisplatin; D005472:Fluorouracil