Enhancement of cytarabine sensitivity in squamous cell carcinoma cell line transfected with deoxycytidine kinase.
BACKGROUND
Cytarabine is the most effective agent known for the treatment of acute myeloid leukemia. Its antitumor effect is expressed by combining with DNA during replication and then destroying the DNA chain. However, cytarabine has only limited activity against most solid tumors, including squamous cell carcinoma of the head and neck. The reason for this is thought to be that in cell lines of solid tumors the expression of cytidine deaminase, an enzyme that degrades cytarabine, is high, whereas the expression of deoxycytidine kinase (dCK), which phosphorylates cytarabine (a prodrug), is weak.


OBJECTIVE
To determine whether head and neck squamous cell carcinomas can be made more sensitive to the cytotoxic effects of cytarabine by shifting the balance from the degradative to the activation pathway.


METHODS
Human SCC-25 squamous carcinoma cells were transfected by either retroviral vector or adenoviral vector containing DCK gene and were identified for dCK expression by Northern blot analysis. In vitro cytotoxic assay after cytarabine exposure was performed using these cells.


RESULTS
Both retroviral and adenoviral vector-mediated transduction of the dCK complementary DNA resulted in marked sensitization of tongue squamous carcinoma cell lines to the cytotoxic effects of cytarabine in vitro.


CONCLUSIONS
The dCK-cytarabine system may be a useful approach for gene therapy of squamous cell carcinomas of the head and neck.
Kojima
Hiromi
H
Department of Otorhinolaryngology, Jikei University School of Medicine, 3-25-8 Nishishinbashi Minato-ku, 105-8461 Tokyo, Japan.
Iida
Minoru
M
Miyazaki
Hidemi
H
Koga
Tomohiko
T
Moriyama
Hiroshi
H
Manome
Yoshinobu
Y
D000256:Adenoviridae; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D003561:Cytarabine / Q000494:pharmacology*; D003842:Deoxycytidine Kinase / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D015316:Genetic Therapy; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D011355:Prodrugs / Q000494:pharmacology*; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D003561:Cytarabine; D003842:Deoxycytidine Kinase