Antitumoral effects of recombinant adenovirus YKL-1001, conditionally replicating in alpha-fetoprotein-producing human liver cancer cells.
Selectively replicating recombinant adenovirus has emerged as a novel strategy for the treatment of incurable human cancers. One of the major characteristics of hepatocellular carcinoma is the transcriptional reactivation of alpha-fetoprotein (AFP). In this study, we evaluated the liver cancer-specific oncolytic potential of E1B 55kDa-deleted recombinant adenovirus (YKL-1001), which retained other E1 genes driven by the AFP promoter. Transient transfection study using luciferase indicated the selective activation of the AFP promoter only in human liver cancer cells secreting AFP (HepG2, Hep3B). YKL-1001 induced both cytopathic effects exclusively in AFP-positive liver cancer cells and the growth inhibition of pre-established Hep3B xenografts. Finally, hematoxylin-eosin staining and the immunohistochemistry to the adenoviral hexon showed a large distributed necrotic area and this implied a wide spread of YKL-1001. Therefore, the present study demonstrated that YKL-1001 holds significant promise as an oncolytic agent for hepatocellular carcinoma.
Kim
Jaesung
J
Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea.
Lee
Boyoung
B
Kim
Jin Seok
JS
Yun
Chae Ok
CO
Kim
Joo Hang
JH
Lee
Yong J
YJ
Joo
Chul Hyun
CH
Lee
Heuiran
H
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D005347:Fibroblasts / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy*; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013997:Time Factors; D015533:Transcriptional Activation; D014466:Ultraviolet Rays; D000509:alpha-Fetoproteins / Q000096:biosynthesis* / Q000235:genetics
D000970:Antineoplastic Agents; D000509:alpha-Fetoproteins; D008156:Luciferases