自噬是一种通过溶酶体途径分解代谢细胞内组分的过程。在细胞应激状态下,细胞通过自噬清除线粒体等损坏的细胞器和蛋白。在肿瘤发生发展的早期和晚期,自噬发挥的作用是不同的:肿瘤发生早期,自噬降低肿瘤原发性基因不稳定性和蛋白聚集,以及激发抗肿瘤性免疫应答;在成熟的肿瘤中,细胞通过自噬对营养不足以及细胞过度增殖所致的代谢应激产生抵抗。自噬不仅促进肿瘤细胞存活,在特殊条件下,也可导致肿瘤细胞自噬性细胞死亡。自噬性细胞死亡可增加发生凋亡的肿瘤细胞对辐射治疗的敏感性。因此,肿瘤发生及肿瘤治疗中自噬的作用是双向的,需要更加
近期,兰州军区乌鲁木齐总院药剂科研究人员发表《自噬在肿瘤耐药中的作用研究进展》研究,该文章发表于2015年3期的《国际药学研究杂志》上。
自噬是一种通过溶酶体途径分解代谢细胞内组分的过程。在细胞应激状态下,细胞通过自噬清除线粒体等损坏的细胞器和蛋白。在肿瘤发生发展的早期和晚期,自噬发挥的作用是不同的:肿瘤发生早期,自噬降低肿瘤原发性基因不稳定性和蛋白聚集,以及激发抗肿瘤性免疫应答;在成熟的肿瘤中,细胞通过自噬对营养不足以及细胞过度增殖所致的代谢应激产生抵抗。自噬不仅促进肿瘤细胞存活,在特殊条件下,也可导致肿瘤细胞自噬性细胞死亡。自噬性细胞死亡可增加发生凋亡的肿瘤细胞对辐射治疗的敏感性。因此,肿瘤发生及肿瘤治疗中自噬的作用是双向的,需要更加深入的研究阐明自噬在肿瘤中发挥作用的详细机制。本文对自噬在肿瘤细胞化疗耐药中发挥作用的研究进展进行综述。
Abstract:
MacroAutophagy is a catabolic pathway that degrades cellular components through the lysosomal machinery. Autophagy acts as a survival mechanism under energy depletion-or nutrition deficiency-caused stress as an intracellular quality management system by clearing damaged organelles like mitochondria and proteins. During the early and late stages of cancer development, the role of autophagy differs. In the very early stages of carcinogenesis, autophagy has an important function by reducing cancer initiating genetic instability and aberrant protein aggregates as well as promoting anti-cancer immune response. In established malignant tumors autophagy confers resistance against metabolic stress caused by nutrient deprivation and the rapid proliferation of carcinoma cells. This function of autophagy is also important for radiation and chemotherapy resistance in cancer. Autophagy not only promotes the survival of tumor cells, but also, in special condition, leads to autophagic tumor cell death. During dysfunctional apoptosis this form of cell death mainly sensitizes cancer cells for therapy such as ionizing radiation. Therefore, the functions of autophagy during cancer progression and therapy are two-sided and further research is needed to understand them in greater detail. In this review, the regulation and the role of autophagy in cancer and chemotherapy resistance are discussed.
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