许多研究已经确定自噬在所有细胞的存活中起着核心作用。包括恶性的。自噬是一般机制中的中心齿轮,其提供决定细胞生理和表型特征的细胞内蛋白稳定。积累的数据表明,自噬在很大程度上有助于癌细胞的干细胞性。因此,自噬调节被认为是针对癌症干细胞消除的治疗中一个有希望的药理学靶点。然而,自噬是一个多阶段的细胞内过程,涉及许多蛋白质参与者。此外,该过程可以由各种信令模块同时激活。因此,选择一种有效的抗自噬药物是一项不小的壮举。更重要的是,寻找潜在的化疗药物,可以通过抑制自噬的药理学作用消除肿瘤干细胞,目前仍在进行中.在目前的工作中,我们选择了一组自噬抑制剂(Autophinib,SBI-0206965,Siramesine,MRT68921和IITZ-01),其中一些最近被确定为癌细胞中有效的自噬抑制剂。使用A549癌细胞,表达核心干因子Oct4和Sox2,我们评估了这些药物对癌症干细胞的存活和保留原始特性的影响。在选定的代理商中,只有Autophinib对肿瘤干细胞有明显的毒性作用.结果表明,Autophinib抑制自噬下调A549细胞中Sox2蛋白的表达,这种下调与细胞凋亡的显著诱导相关。此外,Autophinib处理的A549细胞不能形成球体,这表明干性降低。因此,在研究的药物中,只有Autophinib可以被认为是对抗癌症干细胞的潜在药物.
Numerous studies have already established that autophagy plays a central role in the survival of all cells, including malignant ones. Autophagy is a central cog in the general mechanism that provides the intracellular proteostasis determining cellular physiological and phenotypic characteristics. The accumulated data show that autophagy largely contributes to cancer cell stemness. Thus, autophagy modulation is considered one of the promising pharmacological targets in therapy aimed at cancer stem cell elimination. However, autophagy is a multi-stage intracellular process that involves numerous protein participants. In addition, the process can be activated simultaneously by various signaling modules. Therefore, it is no small feat to select an effective pharmacological drug against autophagy. What\'s more, the search for potential chemotherapeutic agents that could eliminate cancer stem cells through pharmacological inhibition of autophagy is still under way. In the present work, we selected a panel of autophagy inhibitors (
Autophinib, SBI-0206965, Siramesine, MRT68921, and IITZ-01), some of whom have been recently identified as effective autophagy inhibitors in cancer cells. Using A549 cancer cells, which express the core stem factors Oct4 and Sox2, we evaluated the effect of these drugs on the survival and preservation of the original properties of cancer stem cells. Among the agents selected, only
Autophinib demonstrated a significant toxic effect on cancer stem cells. The obtained results demonstrate that autophagy inhibition by
Autophinib downregulates the expression of the Sox2 protein in A549 cells, and that this downregulation correlates with a pronounced induction of apoptosis. Moreover,
Autophinib-treated A549 cells are unable to form spheroids, which indicates a reduction in stemness. Thus, among the drugs studied, only
Autophinib can be considered a potential agent against cancer stem cells.