Zhao Qi, Yang Li-Jun, Zheng Yan-Bo, Gong Jian-Hua
Department of Pharmacology,Shanxi Medical University,Taiyuan 030001,China.
Department of Oncology,Institute of Medicinal Biotechnology,CAMS and PUMC,Beijing 100050,China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2022 Apr;44(2):338-347. doi: 10.3881/j.issn.1000-503X.13241.
Programmed necrosis,a mode of cell death independent of Caspase,is mainly mediated by receptor-interacting protein kinase-1 (RIPK1),receptor-interacting protein kinase-3 (RIPK3),and mixed lineage kinase domain-like protein (MLKL).Studies have demonstrated that programmed necrosis has the dual role of promoting and inhibiting tumor growth and thus we can control the development of tumor by regulating programmed necrosis.The drugs capable of inducing programmed necrosis show potential anti-tumor activity.In addition,inducing programmed necrosis is an effective way to overcome tumor resistance to apoptosis.This paper summarized the mechanisms of programmed necrosis and its relationship with tumors.We focused on the antitumor activity of programmed necrosis inducers including natural products,chemotherapeutic drugs,death receptor ligands,kinase inhibitors,inorganic salts,metal complexes,and metal nanoparticles.These agents will provide new therapeutic candidates for the treatment of tumors,especially the tumors acquiring resistance to apoptosis.
程序性坏死是一种独立于半胱天冬酶的细胞死亡方式,主要由受体相互作用蛋白激酶-1(RIPK1)、受体相互作用蛋白激酶-3(RIPK3)和混合谱系激酶结构域样蛋白(MLKL)介导。研究表明,程序性坏死具有促进和抑制肿瘤生长的双重作用,因此我们可以通过调节程序性坏死来控制肿瘤的发展。能够诱导程序性坏死的药物显示出潜在的抗肿瘤活性。此外,诱导程序性坏死是克服肿瘤细胞凋亡抗性的有效途径。本文总结了程序性坏死的机制及其与肿瘤的关系。我们重点关注了程序性坏死诱导剂的抗肿瘤活性,包括天然产物、化疗药物、死亡受体配体、激酶抑制剂、无机盐、金属配合物和金属纳米颗粒。这些药物将为肿瘤治疗,尤其是对细胞凋亡产生抗性的肿瘤治疗提供新的治疗候选药物。