 |
|
Enhancement of Cytarabine Sensitivity in Squamous Cell Carcinoma Cell Line Transfected With Deoxycytidine Kinase
Hiromi Kojima, MD;
Minoru Iida, MD;
Hidemi Miyazaki, MD;
Tomohiko Koga, MT;
Hiroshi Moriyama, MD;
Yoshinobu Manome, MD
Arch Otolaryngol Head Neck Surg. 2002;128:708-713.
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.
Conclusion The dCK-cytarabine system may be a useful approach for gene therapy
of squamous cell carcinomas of the head and neck.
From the Departments of Otorhinolaryngology (Drs Kojima, Iida, Miyazaki,
and Moriyama) and Microbiology (Dr Manome), Jikei University School of Medicine,
Tokyo, Japan, and the Division of Clinical Laboratory, Chiba Social Insurance
Hospital, Chiba, Japan (Dr Koga).
RELATED ARTICLE
Archives of Otolaryngology–Head & Neck Surgery Reader's Choice: Continuing Medical Education
Arch Otolaryngol Head Neck Surg. 2002;128(6):726-728.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Enhancement of Cisplatin sensitivity in squamous cell carcinoma of the head and neck transfected with a survivin antisense gene.
Kojima et al.
Arch Otolaryngol Head Neck Surg 2006;132:682-685.
ABSTRACT
| FULL TEXT
|
