Sensitization of head and neck squamous cell carcinoma cells to Fas-mediated apoptosis by the inhibition of Bcl-XL 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-XL 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). Methods and 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-XL was greatly reduced in ActD-treated HSC-2. Moreover, the reduction of Bcl-XL by specific antisense oligonucleotide treatment enhanced the CH11-induced cell death of HSC-2. Conclusion: Our data suggest that Fas-signaling might be regulated by a Bcl-XL-inhibitable step in CH11-resistant HSC-2.