Silencing Heat Shock Transcription Factor 1 Using Small Interfering RNA Enhances Mild Hyperthermia and Hyperthermia Sensitivity in Human Oral Squamous Cell Carcinoma Cells

Targeting heat shock transcription factor 1 for novel hyperthermia therapy

“…They concluded that HSF1 function helps to maintain the growth and survival of human cancer cells (27). Similar results were reported when other in vitro experiments were performed using melanoma cells (29,36), OSCC cells (37), pancreatic cancer cells (22) and human epidermal growth factor receptor 2 (HER2)-positive cancer cells (58) (Table II). Although the molecular mechanisms by which HSF1 regulates cellular proliferation and survival in cancer cells are less understood, genome-wide transcriptome studies have indicated that HSF1 regulates numerous other targets in addition to HSPs (25, [59][60][61][62].…”

“…Thus, the combination of HT and HSF1-targeting may be an attractive option and worthy of further investigation. As expected, the inhibition of functions of HSF1 by using gene targeting or HSF1 inhibitors was shown to reduce the acquisition of thermoresistance (30)(31)(32)(33) and to sensitize tumors to HT-induced cell death (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). In the near future, targeting HSF1 (67,68) in combination with HT may come to be a promising approach for the treatment of cancer.…”

“…Of note, targeting of HSF1 has been suggested to enhance the sensitivity to HT under basic experimental conditions (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). We recently showed that silencing HSF1 using small interfering RNA (siRNA) enhances the mild HT (42˚C, 90 min) and HT (44˚C, 90 min) sensitivity in human OSCC cells (37). Significant enhancement of the HT sensitivity has also been observed in HSF1-silenced cervical cancer (35) and melanoma cells (29,36) treated with triptolide, an inhibitor of the human heat shock response, and shRNA for HSF1, respectively.…”

“…Elevation of HSF1 has been observed in several types of human tumor tissues (19)(20)(21)(22)(23)(24)(25)(26), and it has been shown to participate in the initiation, proliferation and maintenance of tumors (12,(25)(26)(27)(28)(29). Notably, both inhibition of the expression of HSF1 and the functional loss of HSF1 have been suggested to enhance the sensitivity to HT under basic experimental conditions (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). In the present review, the physiological and pathological roles of HSF1 in cancer cells are summarized, and the potential of HSF1 as a therapeutic target for HT therapy is discussed.…”

Identification of common gene networks responsive to mild hyperthermia in human cancer cells

“…In addition, the induction of BAG3 is mediated, at least in part, by the activation of HSF1, as in the case of HSPs (54). Of note, the inhibition of the functions of HSF1 (55)(56)(57) or Hsp70 (58) by the use of gene targeting has been shown to sensitize HT-induced cell death in cancer cells. The targeting of heat shock response pathways, including these molecules in combination with HT may become a promising therapeutic approach for the treatment of cancer.…”