靶向电压依赖性阴离子通道-1治疗肿瘤的研究进展

doi:10.16352/j.issn.1001-6325.2026.10.1424

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (10): 1424-1428.doi: 10.16352/j.issn.1001-6325.2026.10.1424

靶向电压依赖性阴离子通道-1治疗肿瘤的研究进展

徐佳爱¹, 郭英¹, 张超², 李贺², 杨春华^1*

1.山东医药大学药学院,山东烟台 264003;
2.山东医药大学烟台附属医院胃肠外科,山东烟台 264003

收稿日期:2025-07-18 修回日期:2025-11-27 出版日期:2026-10-05 发布日期:2026-09-18
通讯作者: ^*yangchunhua@bzmc.edu.cn
基金资助:
山东省自然科学基金(ZR2021MH141,ZR2021MH148)

Research progress in targeting voltage-dependent anion channel-1 for cancer therapy

XU Jiaai¹, GUO Ying¹, ZHANG Chao², LI He², YANG Chunhua^1*

1. College of Pharmacy, Shandong Medical and Pharmaceutical University, Yantai 264003;
2. Department of Gastrointestinal Surgery, Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University, Yantai 264003, China

Received:2025-07-18 Revised:2025-11-27 Online:2026-10-05 Published:2026-09-18
Contact: ^*yangchunhua@bzmc.edu.cn

摘要/Abstract

摘要： 电压依赖性阴离子通道-1(VDAC1)是线粒体功能调控关键因子,在多种肿瘤中高表达且提示不良预后,通过多重机制参与肿瘤进程:介导通道关闭后增强糖酵解、驱动代谢重编程以支撑肿瘤增殖、影响肿瘤微环境;发生寡聚化后增加线粒体通透性,诱导细胞凋亡与铁死亡;还可激活PINK/Parkin依赖的自噬,助力肿瘤细胞存活。当前靶向VDAC1的治疗策略主要包括基于miRNA/siRNA的基因沉默手段降低VDAC1表达水平,使用VDAC1特异靶向药物抑制糖酵解/诱导细胞死亡,以及其他非特异性靶向药物通过VDAC1发挥作用。

关键词: 电压依赖性阴离子通道-1, 代谢重编程, 细胞死亡, 靶向治疗, 肿瘤

Abstract: Voltage-dependent anion channel-1 (VDAC1), a key regulator of mitochondrial function, is highly expressed in various cancers and is associated with poor prognosis. It participates in tumor progression through multiple mechanisms: by enhancing glycolysis upon channel closure, driving metabolic reprogramming to support tumor proliferation, and influencing the tumor microenvironment; upon oligomerization, it increases mitochondrial outer membrane permeability, inducing apoptosis and ferroptosis; and it can also activate PINK1/Parkin-dependent autophagy, promoting tumor cell survival. Current VDAC1-targeted therapeutic strategies primarily include miRNA/siRNA-based gene silencing to reduce VDAC1 expression, VDAC1-specific targeted agents to inhibit glycolysis/induce cell death, and other non-specific targeted drugs that exert effects through VDAC1.

Key words: VDAC1, metabolic reprogramming, cell death, targeted therapy, cancer

中图分类号:

R730

徐佳爱, 郭英, 张超, 李贺, 杨春华. 靶向电压依赖性阴离子通道-1治疗肿瘤的研究进展[J]. 基础医学与临床, 2026, 46(10): 1424-1428.

XU Jiaai, GUO Ying, ZHANG Chao, LI He, YANG Chunhua. Research progress in targeting voltage-dependent anion channel-1 for cancer therapy[J]. Basic & Clinical Medicine, 2026, 46(10): 1424-1428.

参考文献

[1] Karunanithi Nivedita A, Shoshan-Barmatz V. Etoposide-induced cancer cell death: roles of mitochondrial VDAC1 and calpain, and resistance mechanisms[J]. Mol Oncol, 2025, 19: 1855-1875.
[2] Melnikov N, Pittala S, Shteinfer-Kuzmine A, et al. Mitochondrial VDAC1 silencing in urethane-induced lung cancer inhibits tumor growth and alters cancer oncogenic properties[J]. Cancers (Basel), 2024, 16: 2970. doi:10.3390/cancers16172970.
[3] Alhozeel B, Pandey S K, Shteinfer-Kuzmine A, et al. Silencing the mitochondrial gatekeeper VDAC1 as a potential treatment for bladder cancer[J]. Cells, 2024, 13. doi:10.3390/cells13070627.
[4] Yang H, Wang Z, Hu S, et al. miRNA-874-3p inhibits the migration, invasion and proliferation of breast cancer cells by targeting VDAC1[J]. Aging, 2023, 15: 705-717.
[5] Rostovtseva TK, Bezrukov SM. Hoogerheide DP regulation of mitochondrial respiration by VDAC is enhanced by membrane-bound inhibitors with disordered polyanionic C-terminal domains[J]. Int J Mol Sci, 2021, 22:7358. doi:10.3390/ijms22147358.
[6] Wang L, Kong L, Zhang DQ, et al. Inhibiting glycolysis and disrupting the mitochondrial HK2-VDAC1 protein-protein interaction using a bifunctional lonidamine-conjugated metal probe for combating triple-negative breast cancer[J]. J Am Chem Soc, 2025, 147: 14824-14836.
[7] Pandey SK, Machlof-Cohen R, Santhanam M, et al. Silencing VDAC1 to treat mesothelioma cancer: tumor reprograming and altering tumor hallmarks[J]. Biomolecules, 2022, 12: 895. doi:10.3390/biom12070895.
[8] Li J, Wu G, Su H, et al. Hsp90 C-terminal domain inhibition enhances ferroptosis by disrupting GPX4-VDAC1 interaction to increase HMOX1 release from oligomerized VDAC1 channels[J]. Redox Biol, 2025, 85: 103672. doi:10.1016/j.redox.2025.103672.
[9] Zhang J, Liu L, Li Y, et al. HSP90 C-terminal domain inhibition promotes VDAC1 oligomerization via decreasing K274 mono-ubiquitination in hepatocellular carcinoma[J]. Neoplasia, 2023, 44: 100935. doi:10.1016/j.neo.2023.100935.
[10] Wu NN, Wang L, Wang L, et al. Site-specific ubiquitination of VDAC1 restricts its oligomerization and mitochondrial DNA release in liver fibrosis[J]. Exp Mol Med, 2023, 55: 269-280.
[11] Santhanam M, Babu V, Shteinfer-Kuzmine A, et al. VDAC1-interacting proteins: binding site mapping and their derived peptides induce apoptosis and multifaceted cellular effects[J]. Apoptosis, 2025,30:2938-2959. doi:10.1007/s10495-025-02185-y.
[12] Yang J, Lu X, Hao J L, et al. VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis[J]. Nat Commun, 2025, 16: 1160. doi:10.1038/s41467-025-56494-6.
[13] Jang SK, Ahn S H, Kim G, et al. Inhibition of VDAC1 oligomerization blocks cysteine deprivation-induced ferroptosis via mitochondrial ROS suppression[J]. Cell Death Dis, 2024, 15: 811. doi:10.1038/s41419-024-07216-1.
[14] Oflaz FE, Bondarenko AI, Trenker M, et al. Annexin A5 controls VDAC1-dependent mitochondrial Ca²⁺ homeos-tasis and determines cellular susceptibility to apoptosis[J]. EMBO J, 2025, 44: 3413-3447.
[15] Huang H, Chen M, Feng S, et al. The dual role of VDAC in cancer: molecular mechanisms and advances in targeted therapy[J]. Biomed Pharmacother, 2025, 191: 118530. doi:10.1016/j.biopha.2025.118530.
[16] Liu Y, Zhang H, Liu Y, et al. Hypoxia-induced GPCPD1 depalmitoylation triggers mitophagy via regulating PRKN-mediated ubiquitination of VDAC1[J]. Autophagy, 2023, 19: 2443-2463.
[17] Su F, Yu J, Xu S, et al. Hederagenin exerts anti-tumor effects in pancreatic cancer by impairing DRP1 mediated-mitophagy via VDAC1-HK2-PINK1/PARKIN pathway[J]. Toxicol Appl Pharmacol, 2025, 505: 117586. doi:10.1016/j.taap.2025.117586.
[18] Arif T, Shteinfer-Kuzmine A. Shoshan-Barmatz V decod-ing cancer through silencing the mitochondrial gatekeeper VDAC1[J]. Biomolecules, 2024, 14: 1304. doi:10.3390/biom 14101304.
[19] Zheng J, Feng Y. Yuan C Hsa_circ_0007905 as a modulator of miR-330-5p and VDAC1: Enhancing stemness and reducing apoptosis in cervical cancer stem cells[J]. Gen Physiol Biophys, 2025, 44: 213-226.
[20] Sun W, Angelov A, Han X, et al. self-assembling amphiphilic peptides target the VDAC1-Hexokinase-Ⅱ complex to induce apoptosis in cervical carcinoma cells[J]. J Med Chem, 2025, 68:18857-18868.
[21] Shteinfer-Kuzmine A, Amsalem Z, Arif T, et al. Selective induction of cancer cell death by VDAC1-based peptides and their potential use in cancer therapy[J]. Mol Oncol, 2018, 12: 1077-1103.
[22] Zhang K, Yuan B, Dai X, et al. Selection and identification of DNA aptamer binding VDAC1 for tumor tissue imaging and targeted drug delivery[J]. Int J Biol Macromol, 2025, 306: 141249. doi:10.1016/j.ijbiomac.2025.141249.
[23] Hu A, Wang H, Xu Q, et al. A novel CPT1A covalent inhibitor modulates fatty acid oxidation and CPT1A-VDAC1 axis with therapeutic potential for colorectal cancer[J]. Redox Biol, 2023, 68: 102959. doi:10.1016/j.redox.2023.102959.
[24] Shteinfer-Kuzmine A, Moyal M M, Karunanithi Nivedita A, et al. Metformin-induced apoptosis is mediated through mitochondrial VDAC1[J]. Pharmaceuticals (Basel), 2025, 18: 757. doi:10.3390/ph18050757.
[25] Ko M, Kim J, Lazim R, et al. The anticancer effect of metformin targets VDAC1 via ER-mitochondria interac-tions-mediated autophagy in HCC[J]. Exp Mol Med, 2024, 56: 2714-2725.

靶向电压依赖性阴离子通道-1治疗肿瘤的研究进展

Research progress in targeting voltage-dependent anion channel-1 for cancer therapy

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王君, 华祎炜, 赵奕, 刘广华, 东洁. 一例45 cm腹膜后去分化脂肪肉瘤报告[J]. 基础医学与临床, 2026, 46(9): 1272-1276.
[2]	由婷婷, 唐辉, 宋东峰, 应金蓉, 白春梅. 小细胞肺癌诊疗进展[J]. 基础医学与临床, 2026, 46(8): 1149-1153.
[3]	袁静怡, 张旖垚, 刘长征. 蛋白质乳酰化修饰在脓毒症中调控机制的研究进展[J]. 基础医学与临床, 2026, 46(8): 1144-1148.
[4]	杜金知, 倪文洋, 朱荣宇, 孟治寿, 杨建新. 艾司氯胺酮缓解膝骨关节炎大鼠疼痛[J]. 基础医学与临床, 2026, 46(8): 1096-1102.
[5]	熊艳蕾, 王雷明, 李敏, 李倩, 滕梁红. PDCA管理在提升甲状腺细针穿刺细胞学BRAF V600E检测效率中的应用[J]. 基础医学与临床, 2026, 46(8): 1117-1120.
[6]	秦子亿, 徐也婷, 邹佳铭, 马金阳, 王钰铖, 鞠瑞, 郭磊. 羧胺三唑乳清酸盐调控肿瘤相关成纤维细胞功能并重塑胰腺癌微环境[J]. 基础医学与临床, 2026, 46(8): 1068-1075.
[7]	刘睿琦, 张建民, 何维, 陈慧. FBXO2是Vδ1 γδ T细胞识别的肿瘤相关异位蛋白质配体[J]. 基础医学与临床, 2026, 46(7): 887-894.
[8]	李贤群, 池雨欣, 苗家鸣, 齐晓璐, 魏童, 杨卫红. 肿瘤相关内含子增强子区SNPs调控机制的研究进展[J]. 基础医学与临床, 2026, 46(7): 1009-1013.
[9]	刘翠玲, 于树娜. NLRP3炎性小体在肝缺血/再灌注损伤中作用的研究进展[J]. 基础医学与临床, 2026, 46(7): 1004-1008.
[10]	李书翔, 潘玮瑄, 保永莉, 夏婉娉, 李雪媛, 郑永昌, 陈阳. 肝细胞癌肿瘤边界代谢空间异质性研究[J]. 基础医学与临床, 2026, 46(6): 815-822.
[11]	刘承国, 李露, 邹川. 氧化应激在急性脑损伤发病机制中的作用[J]. 基础医学与临床, 2026, 46(5): 721-725.
[12]	张帅, 王腾祺, 田永静, 庞健, 孙海滨, 雷馨文. KRT15调节胃癌免疫微环境并抑制恶性表型[J]. 基础医学与临床, 2026, 46(5): 658-665.
[13]	刘靖靖, 李燕. 脂肪酸代谢重编程在弥漫性大B细胞淋巴瘤中的研究进展[J]. 基础医学与临床, 2026, 46(4): 582-586.
[14]	刘芃芃, 孙昭, 邱维, 唐辉, 朱文佳, 王文惠, 王颖轶. 局部放射治疗对酪氨酸激酶抑制剂治疗非小细胞肺癌伴寡残留病变的影响[J]. 基础医学与临床, 2026, 46(4): 491-497.
[15]	李志涛, 步雪峰, 张拥军, 孟娜娜, 夏磊洲. 法尼酯X受体通过负调控基质金属蛋白酶7抑制胰腺癌细胞增殖[J]. 基础医学与临床, 2026, 46(2): 250-255.