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了解细胞凋亡及靶向癌症治疗的凋亡途径。

Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics.

作者信息

Jan Rehmat, Chaudhry Gul-E-Saba

机构信息

Institute of Marine Biotechnology, Universiti Terengganu Malaysia, 21030 Terengganu, Malaysia.

出版信息

Adv Pharm Bull. 2019 Jun;9(2):205-218. doi: 10.15171/apb.2019.024. Epub 2019 Jun 1.

Abstract

Various physiological processes involve appropriate tissue developmental process and homeostasis - the pathogenesis of several diseases connected with deregulatory apoptosis process. Apoptosis plays a crucial role in maintaining a balance between cell death and division, evasion of apoptosis results in the uncontrolled multiplication of cells leading to different diseases such as cancer. Currently, the development of apoptosis targeting anticancer drugs has gained much interest since cell death induced by apoptosis causes minimal inflammation. The understanding of complexities of apoptosis mechanism and how apoptosis is evolved by tumor cells to oppose cell death has focused research into the new strategies designed to induce apoptosis in cancer cells. This review focused on the underlying mechanism of apoptosis and the dysregulation of apoptosis modulators involved in the extrinsic and intrinsic apoptotic pathway, which include death receptors (DRs) proteins, cellular FLICE inhibitory proteins (c-FLIP), anti-apoptotic Bcl-2 proteins, inhibitors of apoptosis proteins (IAPs), tumor suppressor (p53) in cancer cells along with various current clinical approaches aimed to selectively induce apoptosis in cancer cells.

摘要

各种生理过程涉及适当的组织发育过程和内环境稳态——几种与凋亡调控异常过程相关疾病的发病机制。凋亡在维持细胞死亡与分裂之间的平衡中起着关键作用,逃避凋亡会导致细胞不受控制地增殖,从而引发不同疾病,如癌症。目前,靶向凋亡的抗癌药物的研发备受关注,因为凋亡诱导的细胞死亡引起的炎症最小。对凋亡机制的复杂性以及肿瘤细胞如何通过凋亡来抵抗细胞死亡的理解,促使人们将研究重点放在旨在诱导癌细胞凋亡的新策略上。本综述聚焦于凋亡的潜在机制以及参与外源性和内源性凋亡途径的凋亡调节因子的失调,这些调节因子包括死亡受体(DRs)蛋白、细胞FLICE抑制蛋白(c-FLIP)、抗凋亡Bcl-2蛋白、凋亡抑制蛋白(IAPs)、癌细胞中的肿瘤抑制因子(p53),以及目前旨在选择性诱导癌细胞凋亡的各种临床方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c59/6664112/6095d7dc2f17/apb-9-205-g001.jpg

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