Nifuroxazide suppresses PD-L1 expression and enhances the efficacy of radiotherapy in hepatocellular carcinoma

被引:5
|
作者
Zhao, Tiesuo [1 ,2 ,3 ]
Wei, Pengkun [1 ,2 ,4 ]
Zhang, Congli [1 ,2 ]
Zhou, Shijie [1 ,2 ]
Liang, Lirui [1 ,2 ]
Guo, Shuoshuo [1 ,2 ]
Yin, Zhinan [5 ]
Cheng, Sichang [1 ,2 ]
Gan, Zerui [1 ,2 ]
Xia, Yuanling [1 ,2 ]
Zhang, Yongxi [6 ]
Guo, Sheng [1 ,2 ]
Zhong, Jiateng [2 ]
Yang, Zishan [1 ,2 ]
Tu, Fei [2 ]
Wang, Qianqing [7 ,8 ]
Bai, Jin [7 ,8 ]
Ren, Feng [3 ]
Feng, Zhiwei [1 ,2 ]
Jia, Huijie [2 ]
机构
[1] Xinxiang Med Univ, Sch Basic Med Sci, Dept Immunol, Xinxiang, Peoples R China
[2] Xinxiang Med Univ, Xinxiang Engn Technol Res Ctr Immune Checkpoint Dr, Xinxiang, Peoples R China
[3] Xinxiang Med Univ, Henan Int Joint Lab Immun & Targeted Therapy Liver, Xinxiang, Peoples R China
[4] Zhengzhou Univ, Zhengzhou Cent Hosp, Zhengzhou, Peoples R China
[5] Jinan Univ, Biomed Translat Res Inst, Fac Med Sci, Guangzhou, Peoples R China
[6] Xinxiang Med Univ, Affiliated Hosp 3, Dept Oncol, Xinxiang, Peoples R China
[7] Xinxiang Cent Hosp, Dept Gynecol, Xinxiang, Peoples R China
[8] Xinxiang Med Univ, Clin Coll 4, Xinxiang, Peoples R China
来源
ELIFE | 2024年 / 12卷
关键词
hepatocellular carcinoma; PD-L1; radiotherapy; cancer immunotherapy; Mouse;
D O I
10.7554/eLife.90911
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Radiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression. Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosis in vitro. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.
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页数:22
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