Parkin enhances sensitivity of paclitaxel to nasopharyngeal carcinoma by activating BNIP3/NIX-mediated mitochondrial autophagy

被引:0
|
作者
Ni, Haifeng [1 ]
Liu, Renhui [2 ]
Zhou, Zhen [1 ]
Jiang, Bo [1 ]
Wang, Bin [1 ]
机构
[1] Zhejiang Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, Dept Otolaryngol Head & Neck Surg, 261 Huan Sha Rd, Hangzhou 310006, Zhejiang, Peoples R China
[2] Jiange Peoples Hosp, Dept Otolaryngol Head & Neck Surg, Jiange, Sichuan, Peoples R China
来源
CHINESE JOURNAL OF PHYSIOLOGY | 2023年 / 66卷 / 06期
关键词
BNIP3/NIX; mitochondrial autophagy; nasopharyngeal carcinoma; paclitaxel; Parkin; MITOPHAGY; INHIBITION; NIX;
D O I
10.4103/cjop.CJOP-D-23-00076
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
As a malignant head and neck cancer, nasopharyngeal carcinoma (NPC) has high morbidity. Parkin expression has been reported to be reduced in NPC tissues and its upregulation could enhance paclitaxel-resistant cell cycle arrest. This study was performed to explore the possible mechanism of Parkin related to B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa interacting protein 3 (BNIP3)/BNIP3-like (NIX)-mediated mitochondrial autophagy in NPC cells. Initially, after Parkin overexpression or silencing, cell viability and proliferation were evaluated by lactate dehydrogenase and colony formation assays. JC-1 staining was used to assess the mitochondrial membrane potential. In addition, the levels of cellular reactive oxygen species (ROS) and mitochondrial ROS were detected using DCFH-DA staining and mitochondrial ROS (MitoSOX) red staining. The expression of proteins was measured using Western blot. Results showed that Parkin overexpression inhibited, whereas Parkin knockdown promoted the proliferation of paclitaxel-treated NPC cells. Besides, Parkin overexpression induced, whereas Parkin knockdown inhibited mitochondrial apoptosis in paclitaxel-treated NPC cells, as evidenced by the changes of Cytochrome C (mitochondria), Cytochrome C (cytoplasm), BAK, and Bcl-2 expression. Moreover, the levels of ROS, mitochondrial membrane potential, and LC3II/LC3I in paclitaxel-treated C666-1 cells were hugely elevated by Parkin overexpression and were all declined by Parkin knockdown in CNE-3 cells. Furthermore, Parkin upregulation activated, whereas Parkin downregulation inactivated BNIP3/NIX signaling. Further, BNIP3 silencing or overexpression reversed the impacts of Parkin upregulation or downregulation on the proliferation and mitochondrial apoptosis of paclitaxel-treated NPC cells. Particularly, Mdivi-1 (mitophagy inhibitor) or rapamycin (an activator of autophagy) exerted the same effects on NPC cells as BNIP3 silencing or overexpression, respectively. Collectively, Parkin overexpression activated BNIP3/NIX-mediated mitochondrial autophagy to enhance sensitivity to paclitaxel in NPC.
引用
收藏
页码:503 / 515
页数:13
相关论文
共 23 条
  • [1] Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX
    Ney, Paul A.
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2015, 1853 (10): : 2775 - 2783
  • [2] Exercise training and dietary restriction affect PINK1/Parkin and Bnip3/Nix-mediated cardiac mitophagy in mice
    Zhao, Yongcai
    Zhu, Qiaodi
    Song, Wenjuan
    Gao, Binghong
    [J]. GENERAL PHYSIOLOGY AND BIOPHYSICS, 2018, 37 (06) : 657 - 666
  • [3] Tanshinone I inhibits metastasis of cervical cancer cells by inducing BNIP3/NIX-mediated mitophagy and reprogramming mitochondrial metabolism
    Cui, Shuna
    Chen, Tingting
    Wang, Mengmeng
    Chen, Yuanyuan
    Zheng, Qi
    Feng, Xinyi
    Li, Shihua
    Wang, Junsong
    [J]. PHYTOMEDICINE, 2022, 98
  • [4] Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes
    Lee, Youngil
    Lee, Hwa-Youn
    Hanna, Rita A.
    Gustafsson, Asa B.
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2011, 301 (05): : H1924 - H1931
  • [5] Mitochondrial Autophagy Proteins Bnip3 and Nix Maintain Memory B Cell Survival.
    Kodali, S.
    Sandoval, H.
    Chen, M.
    Wang, J.
    [J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2018, 18 : 317 - 317
  • [6] Bnip3/Nix-mediated mitophagy protects memory B cells by restricting de novo fatty acid synthesis
    Kodali, Srikanth
    [J]. JOURNAL OF IMMUNOLOGY, 2020, 204 (01):
  • [7] Mitochondrial adaptations to exercise do not require Bcl2-mediated autophagy but occur with BNIP3/Parkin activation
    Ehrlicher, Sarah E.
    Stierwalt, Harrison D.
    Miller, Benjamin F.
    Newsom, Sean A.
    Robinson, Matthew M.
    [J]. FASEB JOURNAL, 2020, 34 (03): : 4602 - 4618
  • [8] Polystyrene nanoparticles induced mammalian intestine damage caused by blockage of BNIP3/NIX-mediated mitophagy and gut microbiota alteration
    Zhang, Yilun
    Jia, Zhenzhen
    Gao, Xianlei
    Zhao, Juan
    Zhang, Hongyan
    [J]. SCIENCE OF THE TOTAL ENVIRONMENT, 2024, 907
  • [9] Rhopaloic acid A triggers mitochondria damage-induced apoptosis in oral cancer by JNK/BNIP3/Nix-mediated mitophagy
    Chen, Wu-Fu
    Tsai, Sheng-Chieh
    Zhang, Ya-Hui
    Chang, Hui-Min
    Wu, Wan-Ju
    Su, Jui-Hsin
    Wu, Bin-Nan
    Chen, Chung-Yi
    Lin, Mei-Ying
    Chen, Hsien-Lin
    Lee, Chien-Hsing
    [J]. PHYTOMEDICINE, 2024, 132
  • [10] Mitophagy mediated by BNIP3 and NIX protects against ferroptosis by downregulating mitochondrial reactive oxygen species
    Yamashita, Shun-ichi
    Sugiura, Yuki
    Matsuoka, Yuta
    Maeda, Rae
    Inoue, Keiichi
    Furukawa, Kentaro
    Fukuda, Tomoyuki
    Chan, David C.
    Kanki, Tomotake
    [J]. CELL DEATH AND DIFFERENTIATION, 2024, 31 (05): : 651 - 661