期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 15, 期 3, 页码 568-578出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.29759
关键词
Heme oxygenase-1; autophagy; hyperthermia; cervical cancer; human papillomavirus
资金
- National Natural Science Foundation of China [81803148]
- Clinical Research Center of Liaoning Province [2015225012]
- National Key R&D Program of China [2016YFC1302400]
- Ministry of education innovation team development plan The Ministry of education innovation team development plan [IRT_17R107, IRT13101]
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.
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