Inhibiting autophagy before it starts
Inhibiting autophagy before it starts
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DOI：
10.1080/15548627.2023.2197364
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发表时间：
2023-04-10
期刊：
影响因子：
13.3
通讯作者：
Wang, Jing
中科院分区：
文献类型：
--
作者：
Lin, Yuqi;Yu, Biao;Wang, Jing
自噬是一种重要的细胞应激反应机制，常被各种癌细胞利用以在诸如营养缺乏和缺氧的应激下维持快速生长。自噬在肿瘤对化疗、放疗或靶向治疗的抵抗中也起着关键作用。因此，抑制自噬是一种有前途的肿瘤治疗策略。然而，仍然缺乏适合临床使用的有效的自噬抑制剂。大多数药物开发都集中在VPS34和ULK1激酶或半胱氨酸蛋白酶ATG4B等酶上，这些酶在自噬中起着不同的作用。我们发现了一种药物分子艾曲泊帕，通过直接抑制TFEB（转录因子EB），在转录水平抑制自噬溶酶体基因的表达，在转录水平这些蛋白质的合成尚未真正开始。这种药物可以提高替莫唑胺对胶质母细胞瘤治疗的疗效，进一步证实了抑制自噬在癌症治疗中的价值。
Autophagy, an important cellular stress response mechanism, is often exploited by a variety of cancer cells to sustain rapid growth under stresses such as nutrient deprivation and hypoxia. Autophagy also plays a key role in tumor resistance to chemotherapy, radiotherapy or targeted therapy. Inhibition of autophagy is therefore a promising tumor treatment strategy. However, there is still a lack of effective autophagy inhibitors suitable for clinical use. Most drug development has focused on enzymes like the VPS34 and ULK1 kinases, or the cysteine protease ATG4B, which plays different roles in autophagy. We discovered a drug molecule Eltrombopag that inhibits the expression of autophagic lysosomal genes at the stage of transcriptional level, where the synthesis of these proteins has not really begun, by directly inhibiting the TFEB (transcription factor EB). This drug can improve the therapeutic effect of Temozolomide on glioblastoma treatment, further confirming the value of inhibiting autophagy in the treatment of cancer.