Down‐regulation of heat‐shock protein 27–induced resistance to photodynamic therapy in oral cancer cells

Abstract

Photodynamic therapy (PDT) of cells is a new treatment modality involving selective delivery of a photosensitive dye into target cells, followed by visible light irradiation. PDT induces cell death by excessive ROS generation. The effects of multiple photosensitizers were owing to the difference in cell types involving sensitizer-specific protein changes linked to resistance. HSP27 is regulated in response to stress and is associated with apoptotic process. The effects of HSP27 on PDT resistance are controversial and unclear. The purpose of this study was to investigate the role of HSP27 down-regulation in the PDT-induced cells and HSP27 regulation in the resistance to PDT. KB cells transfected with HSP27 siRNA were exposed to hematoporphyrin (HP) followed by irradiation at 635 nm at an energy density of 4.5 mW/cm(2). After irradiation, the effects on HSP27 down-regulation were assessed by MTT assay, flow cytometry, confocal analysis, Western blotting and caspase activity. The results of this study showed that down-regulation of HSP27 restored cell survival in HP-PDT-induced apoptotic KB cells. HSP27 down-regulation attenuated PDT-induced apoptosis through caspase-mediated pathway in KB cells. Also, HSP27 silencing regulated Bax, Bcl-2, and PARP protein expression in PDT-induced cells. Therefore, HSP27 down-regulation confers resistance to PDT through interruption of apoptotic protein activity in PDT-induced cell death. HSP27 might contribute to regulating PDT-induced apoptosis in PDT-resistant cells.

Heat shock proteins in the context of photodynamic therapy: autophagy, apoptosis and immunogenic cell death

“…HSP27 can also inhibit apoptosis by either inhibiting the release of mitochondrial cytochrome c or by binding directly to cytochrome c (Figure 2)(62).The effects of HSP27 on PDT response are controversial and unclear. On the contrary, in human oral cancer cells, the silencing of HSP27 attenuated apoptosis through the caspase-mediated pathway and regulated Bax, Bcl-2 and PARP protein expression in PDT-treated cells employing hematoporphyrin(64). On the contrary, in human oral cancer cells, the silencing of HSP27 attenuated apoptosis through the caspase-mediated pathway and regulated Bax, Bcl-2 and PARP protein expression in PDT-treated cells employing hematoporphyrin(64).…”

Heat Shock Protein 27, a Novel Regulator of Transforming Growth Factor β Induced Resistance to Cisplatin in A549 Cell

“…Accumulated evidences indicated that TGF-β stimulates various genes expression in lung fibroblast and epithelium during fibrogenesis [11], lung injury [12,] and tumorigenesis [8]. Among those genes, heat-shock protein 27 (HSP27), has been identified as an important regulator involved in the development of various cancers and chemoresistance during drug treatment [13,14,15]. HSP27 was highly expressed in mouse lung cancer tissues by the overexpression of HSP27 promoted cell proliferation via the activation of activator protein-1 signaling pathway [16].…”

Avaliação De Proteínas De Choque Térmico Em Células Neoplásicas De Laringe (Hep-2) Após Tratamento Fotodinâmico

“…Os inibidores de HSP90 estão sendo desenvolvidos como agentes anticancerígenos e mostraram bons resultados em tumores sólidos e algumas malignidades hematológicas (RODRÍGUEZ et al, 2016). Kim et al (2012), os resultados obtidos foram pró-tumorais, mostrando que a redução de HSP27 após TFD restaurou a sobrevivência celular por estimular a autofagia e atenuou a apoptose por inibir a via mediada por caspases. Outro estudo realizado por Kim e colaboradores (2016), investigando HSP27, HSP70 e HSP90 após TFD em câncer de cabeça e pescoço, observaram que houve redução de HSP27 e aumento de HSP70 e HSP90, o que resultou em aumento da sobrevida.…”