Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect.
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
Author Information
Yang Yang: Department of Dermatology, No.1 Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang 110001, China.
He-Xiao Wang: Department of Dermatology, No.1 Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang 110001, China.
Lan Zhang: Department of Dermatology, No.1 Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang 110001, China.
Wei Huo: Department of Dermatology, No.1 Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang 110001, China.
Xiao-Dong Li: Department of Dermatology, Central Hospital Affiliated to Shen Yang Medical College, Shenyang, 110001, China.
Rui-Qun Qi: Department of Dermatology, No.1 Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang 110001, China.
Xiao-Yu Song: Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, 110122, China.
Shi Wei: Department of Pathology, the University of Alabama at Birmingham, Birmingham, Alabama 35249, United States.
Xing-Hua Gao: Department of Dermatology, No.1 Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang 110001, China.
Shuai Han: Department of Neurosurgery, No.1 Hospital of China Medical University, Shenyang 110001, China.
Liu Cao: Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, 110122, China.
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.
