Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect
Autor: | Liu Cao, He-Xiao Wang, Wei Huo, Xing-Hua Gao, Yang Yang, Xiao-Dong Li, Ruiqun Qi, Shi Wei, Shuai Han, Xiaoyu Song, Lan Zhang |
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Rok vydání: | 2019 |
Předmět: |
Hyperthermia
autophagy Cell Survival cervical cancer Blotting Western Cell Uterine Cervical Neoplasms Apoptosis Real-Time Polymerase Chain Reaction Inhibitor of apoptosis Applied Microbiology and Biotechnology 03 medical and health sciences Downregulation and upregulation Tandem Mass Spectrometry medicine Humans Viability assay human papillomavirus Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology 0303 health sciences Chemistry Autophagy Cell Biology Flow Cytometry hyperthermia medicine.disease Heme oxygenase Oxidative Stress medicine.anatomical_structure Heme oxygenase-1 Cancer research Female Chromatography Liquid Research Paper Developmental Biology |
Zdroj: | International Journal of Biological Sciences |
ISSN: | 1449-2288 |
Popis: | Hyperthermia has been clinically utilized as an adjuvant therapy in the treatment of cervical carcinoma. However, thermotolerance induced by heme oxygenase-1 (HO-1), a stress-inducible cytoprotective protein, limits the efficacy of hyperthermic therapy, for which the exact mechanism remains unknown. In the present study, we found that heat treatment induced HO-1 expression and decreased copy number of HPV16 in cervical cancer cells and tissues from cervical cancer and precursor lesions. Knockdown of HO-1 stimulated autophagy accompanied by downregulation of X-linked inhibitor of apoptosis protein. Furthermore, silencing of HO-1 led to cell intolerance to hyperthermia, as manifested by inhibition of cell viability and induction of autophagic apoptosis. Moreover, HO-1 modulated hyperthermia-induced, autophagy-dependent antiviral effect. Thus, the findings indicate that blockade of HO-1 enhances hyperthermia-induced autophagy, an event resulting in apoptosis of cervical cancer cells through an antiviral mechanism. These observations imply the potential clinical utility of hyperthermia in combination with HO-1 inhibition in the treatment of cervical cancer. |
Databáze: | OpenAIRE |
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