Hyperthermia is used as one of the treatment modalities for various types of cancer, but the acquisition of thermotolerance in cancer cells, through the induction of
heat shock proteins (Hsps), renders
hyperthermia less effective. Among the Hsp family members,
Hsp27 is frequently associated with thermotolerance and chemoresistance. Thus, down-regulation of
Hsp27 expression during hyperthermic or
chemotherapeutic applications is a promising approach to efficient
tumor treatment. In the present study, we found that the
cytokine interferon-gamma (
IFN-gamma) suppresses the basal, the heat shock-induced and the cisplatin-induced expression of
Hsp27 in HSC-2 (oral
squamous carcinoma) and
A549 (
lung cancer) cells but not in 16HBE14o- (normal
bronchial epithelial cells). Neither
IFN-alpha nor IFN-beta affected
Hsp27 expression, suggesting the specificity of
IFN-gamma. We also demonstrate here that
IFN-gamma suppresses
Hsp27 basal transcription and
promoter activity, and this is mediated specifically through one of the two
Sp1 sites in the
proximal region of the
Hsp27 promoter. More importantly, pre-treatment of cells with
IFN-gamma enhanced the induction of
cell death by
hyperthermia and
cisplatin treatments in the
tumor cell lines, HSC-2 and
A549, but has no effect in 16HBE14o-, indicating a
tumor cell-specific effect of
IFN-gamma. Furthermore, the combination treatment of
hyperthermia and
IFN-gamma suppressed
tumor growth in vivo more effectively than
hyperthermia treatment alone. Together, our findings propose that
IFN-gamma could be a useful
potentiator of
hyperthermia and
cisplatin in cancer therapy.
