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Int J Biol Sci 2019; 15(3):568-578. doi:10.7150/ijbs.29759 This issue Cite

Research Paper

Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect

Yang Yang1,3, He-Xiao Wang1, Lan Zhang1, Wei Huo1, Xiao-Dong Li2, Rui-Qun Qi1, Xiao-Yu Song3, Shi Wei4, Xing-Hua Gao1, Shuai Han5✉, Liu Cao3✉

1. 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
2. Department of Dermatology, Central Hospital Affiliated to Shen Yang Medical College, Shenyang, 110001, China
3. Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, 110122, China
4. Department of Pathology, the University of Alabama at Birmingham, Birmingham, Alabama 35249, United States
5. Department of Neurosurgery, No.1 Hospital of China Medical University, Shenyang 110001, China

✉ Corresponding authors: Liu Cao, Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, China Medical University; Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Preven More

Citation:
Yang Y, Wang HX, Zhang L, Huo W, Li XD, Qi RQ, Song XY, Wei S, Gao XH, Han S, Cao L. Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect. Int J Biol Sci 2019; 15(3):568-578. doi:10.7150/ijbs.29759. https://www.ijbs.com/v15p0568.htm
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Abstract

Graphic 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.

Keywords: Heme oxygenase-1, autophagy, hyperthermia, cervical cancer, human papillomavirus

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APA
Yang, Y., Wang, H.X., Zhang, L., Huo, W., Li, X.D., Qi, R.Q., Song, X.Y., Wei, S., Gao, X.H., Han, S., Cao, L. (2019). Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect. International Journal of Biological Sciences, 15(3), 568-578. https://doi.org/10.7150/ijbs.29759.

ACS
Yang, Y.; Wang, H.X.; Zhang, L.; Huo, W.; Li, X.D.; Qi, R.Q.; Song, X.Y.; Wei, S.; Gao, X.H.; Han, S.; Cao, L. Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect. Int. J. Biol. Sci. 2019, 15 (3), 568-578. DOI: 10.7150/ijbs.29759.

NLM
Yang Y, Wang HX, Zhang L, Huo W, Li XD, Qi RQ, Song XY, Wei S, Gao XH, Han S, Cao L. Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect. Int J Biol Sci 2019; 15(3):568-578. doi:10.7150/ijbs.29759. https://www.ijbs.com/v15p0568.htm

CSE
Yang Y, Wang HX, Zhang L, Huo W, Li XD, Qi RQ, Song XY, Wei S, Gao XH, Han S, Cao L. 2019. Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect. Int J Biol Sci. 15(3):568-578.

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