Oncolysis of human gastric cancers by an E1B 55 kDa-deleted YKL-1 adenovirus.
Advanced gastric cancer cannot be treated with surgery or conventional cancer therapy, which has prompted a search for new therapeutic modalities. Previously, we and other groups showed that E1B 55 kDa-deleted recombinant adenoviruses, such as YKL-1, effectively replicate and induce cytotoxicity in p53-deficient cancer cells while sparing normal cells. Here, we investigated selective YKL-1 replication and resultant cytolysis in human gastric cancer cells. The cytopathic effects were obvious in all five gastric cancer cell lines we examined. Evaluation of p53 expression indicated that only the AGS cell line retained functionally normal p53. Nevertheless, AGS was 10-fold more sensitive to YKL-1 than the other cell lines. Transmission electron microscopy showed typical morphological alterations along with efficient replication of YKL-1 in AGS cells. Therefore, YKL-1 induces preferential cytotoxic effects in human gastric cancer cells in a p53-independent manner, making YKL-1 a promising therapeutic agent for human gastric cancers.
Lee
Boyoung
B
Department of Microbiology, University of Ulsan College of Medicine, P.O. Box 145, 138-736, Seoul, South Korea.
Choi
Jene
J
Kim
Jaesung
J
Kim
Joo-Hang
JH
Joo
Chul Hyun
CH
Cho
Young Keol
YK
Kim
Yoo Kyum
YK
Lee
Heuiran
H
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D017501:Adenovirus E1B Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000260:Adenoviruses, Human / Q000235:genetics* / Q000502:physiology; D001665:Binding Sites / Q000235:genetics; D002166:Camptothecin / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D004274:DNA, Recombinant / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D017353:Gene Deletion; D016158:Genes, p53; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011485:Protein Binding; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014779:Virus Replication
D017501:Adenovirus E1B Proteins; D004274:DNA, Recombinant; D004279:DNA, Viral; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D002166:Camptothecin