Sensitization of head and neck squamous cell carcinoma cells to Fas-mediated apoptosis by the inhibition of Bcl-X(L) expression.
BACKGROUND
Various types of malignant tumor cells are known to acquire resistance to Fas receptor (Fas)-mediated apoptosis. In Fas-sensitive cells, Fas-mediated apoptosis is observed when anti-Fas antibody is bound to Fas. Bcl-2 and Bcl-X(L) are representative anti-apoptosis proteins reported to be capable of suppressing Fas-mediated apoptosis.


OBJECTIVE
To investigate the mechanism of resistance acquisition to Fas-mediated apoptosis in cultured human head and neck squamous cell carcinoma cells (HNSCCs).


RESULTS
We applied an anti-Fas antibody (CH11) to Fas-expressing HNSCCs (HSC-2) and the CH11 did not induce cell death in HSC-2. Treatment with actinomycin D (ActD) converted the phenotypes of HSC-2 from CH11-resistant to CH11-sensitive. Western blot analysis showed no differences between ActD-treated and ActD-untreated HSC-2 in the expression of Bcl-2. On the other hand, the expression of Bcl-X(L) was greatly reduced in ActD-treated HSC-2. Moreover, the reduction of Bcl-X(L) by specific antisense oligonucleotide treatment enhanced the CH11-induced cell death of HSC-2.


CONCLUSIONS
Our data suggest that Fas-signaling might be regulated by a Bcl-X(L)-inhibitable step in CH11-resistant HSC-2.
Otani
Yoshihiro
Y
Department of Otolaryngology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, 216-8511, Kawasaki, Japan.
Tsutsumi
Kouichiro
K
Kuwahara
Daisuke
D
Oyake
Daisuke
D
Ohta
Tomohiko
T
Nishikawa
Hiroyuki
H
Koizuka
Izumi
I
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000503:physiopathology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D010039:Otorhinolaryngologic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000502:physiology*; D051020:bcl-X Protein; D019014:fas Receptor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; C411023:anti-Fas monoclonal antibody; D051020:bcl-X Protein; D019014:fas Receptor