Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect.
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| Abstract |
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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| Authors | Yang Yang, He-Xiao Wang, Lan Zhang, Wei Huo, Xiao-Dong Li, Rui-Qun Qi, Xiao-Yu Song, Shi Wei, Xing-Hua Gao, Shuai Han, Liu Cao |
| Journal | International journal of biological sciences (Int J Biol Sci) Vol. 15 Issue 3 Pg. 568-578 ( 2019) ISSN: 1449-2288 [Electronic] Australia |
| PMID | 30745843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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