摘要
自噬是溶酶体降解途径之一,细胞利用自噬维持着胞内大分子和细胞器的循环利用。自噬的功能主要是在营养缺乏状态下维持着细胞代谢的平衡以及在环境压力下清除损伤的细胞器以利于细胞的存活。如今,自噬又显示出其抑制肿瘤的作用。自噬的缺失经常伴随着肿瘤的发生,比如在乳腺癌、卵巢癌和前列腺癌中出现自噬调节基因beclin 1的缺失,而beclin1基因敲除的小鼠更表现出癌变倾向。自噬是怎样抑制肿瘤发生的是当前生命科学界最感兴趣的课题之一,到目前为止,人们已发现细胞自发机制(涉及染色体完整性和稳定性的保护)和非细胞自发机制(涉及坏死和炎症的抑制)参与其中。在治疗过程中,自噬的作用也非常复杂,一方面,由于肿瘤细胞能够依赖自噬功能来缓解由药物和射线诱导的压力而利于自身存活,所以,在化疗和放疗的同时应用自噬的抑制剂被视为当今癌症治疗的一个新手段,另一方面,诱导自噬可以维持细胞内蛋白质和细胞器的更新、抑制DNA的损伤和染色体的突变并且能限制由坏死引起的炎症而实现细胞的适应性,因而,诱导自噬可能在癌症的预防中扮演着重要的角色。
Autophagy is one of the lysosomal degradation pathway. The autophagy cells maintain the use of macromolecules and organelles recycling. The main function of autophagy is to maintain cellular metabolism under starvation conditions and to clean damaged organelles under stress conditions for the survival of cells. Recently, autophagy has shown its role in tumor suppression. Defective autophagy is linked to the tumorigenesis, as the deletion of the esssential autophagy regulator beclin 1 is detected in human breast, ovarian and prostate cancers and the beclin 1 knockout mice show much more tumor-prone. How autophagy suppresses tumorigenesis have became one of the most interesting topics. Cell-autonomous mechanisms, including the protection of genome stability and intergrity, and a non-cell-autonomous, including the suppression of inflammation and necrosis, have been found so far. The role of autophagy is also very complex in the course of treatment. As the tumor cells depend on autophagy for survival under drug-and radiation-induced stress, the combination of chemotherapy or radiotherapy with an autophagy block has become a novel approach in cancer treatment. On the other hand,the activation of autophagy has shown the effect on maintaining the cellular proteins and organeles update, suppressing the DNA damage and genomic instability, and limiting the necrosis-associated inflammation. These effects may play a critical role in cancer prevention.
出处
《安徽医药》
CAS
2010年第8期869-874,共6页
Anhui Medical and Pharmaceutical Journal
基金
国家科技重大专项课题-重大新药创制项目(No2009ZX09103-399)
关键词
自噬
癌症治疗
细胞死亡
细胞存活
autophagy
cancer-therapy
cell death
cell survival
