Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect
Inhibition of Heme Oxygenase-1 enhances hyperthermia-induced autophagy and antiviral effect
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抑制 Heme Oxygenase-1 可增强热疗诱导的自噬和抗病毒作用
DOI：
10.7150/ijbs.29759
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发表时间：
2019-01
影响因子：
9.2
通讯作者：
Cao Liu
中科院分区：
文献类型：
--
作者：
Yang Yang;Wang He-Xiao;Zhang Lan;Huo Wei;Li Xiao-Dong;Qi Rui-Qun;Song Xiao-Yu;Wei Shi;Gao Xing-Hua;Han Shuai;Cao Liu
热疗已被临床用作宫颈癌的辅助治疗。然而，由血红素氧合酶-1（HO-1），一种应激诱导的细胞保护蛋白诱导的热耐受限制了热疗的疗效，其确切机制仍不清楚。在本研究中，我们发现，热处理诱导HO-1的表达和减少HPV 16的拷贝数在宫颈癌细胞和组织从宫颈癌和前病变。HO-1的敲低刺激自噬伴随着X连锁凋亡抑制蛋白的下调。此外，HO-1沉默导致细胞对高温的不耐受，表现为抑制细胞活力和诱导自噬性凋亡。此外，HO-1调制高血压诱导的，自噬依赖的抗病毒作用。因此，研究结果表明，阻断HO-1可增强高脂血症诱导的自噬，这是一种通过抗病毒机制导致宫颈癌细胞凋亡的事件。这些观察结果暗示了热疗结合HO-1抑制剂在宫颈癌治疗中的潜在临床效用。
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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影响因子：
9.2
作者：
Lv H;Yu Z;Zheng Y;Wang L;Qin X;Cheng G;Ci X
通讯作者：
Ci X
影响因子：
1.3
作者：
Akinfolarin AC;Olusegun AK;Omoladun O;Omoniyi-Esan GO;Onwundiegu U
通讯作者：
Onwundiegu U
影响因子：
--
作者：
Wang HX;Yang Y;Guo H;Hou DD;Zheng S;Hong YX;Cai YF;Huo W;Qi RQ;Zhang L;Chen HD;Gao XH
通讯作者：
Gao XH
血红素加氧酶-1在卡波西肉瘤相关疱疹病毒发病机制和致瘤性中的作用
影响因子：
--
作者：
Dai L;Qiao J;Nguyen D;Struckhoff AP;Doyle L;Bonstaff K;Del Valle L;Parsons C;Toole BP;Renne R;Qin Z
通讯作者：
Qin Z
影响因子：
5.3
作者：
S. Bellanger;Chye Ling Tan;Yuezhen Xue;S. Teissier;F. Thierry
通讯作者：
S. Bellanger;Chye Ling Tan;Yuezhen Xue;S. Teissier;F. Thierry