School of Basic Medicine, Shaoyang University, Shaoyang, 422000, Hunan, China.
College of Medical Technology, Shaoyang University, Shaoyang, 422000, Hunan, China.
Apoptosis. 2022 Oct;27(9-10):647-667. doi: 10.1007/s10495-022-01750-z. Epub 2022 Jul 18.
Chemoresistance of cancer cells is a major problem in treating cancer. Knowledge of how cancer cells may die or resist cancer drugs is critical to providing certain strategies to overcome tumour resistance to treatment. Paclitaxel is known as a chemotherapy drug that can suppress the proliferation of cancer cells by inducing cell cycle arrest and induction of mitotic catastrophe. However, today, it is well known that paclitaxel can induce multiple kinds of cell death in cancers. Besides the induction of mitotic catastrophe that occurs during mitosis, paclitaxel has been shown to induce the expression of several pro-apoptosis mediators. It also can modulate the activity of anti-apoptosis mediators. However, certain cell-killing mechanisms such as senescence and autophagy can increase resistance to paclitaxel. This review focuses on the mechanisms of cell death, including apoptosis, mitotic catastrophe, senescence, autophagic cell death, pyroptosis, etc., following paclitaxel treatment. In addition, mechanisms of resistance to cell death due to exposure to paclitaxel and the use of combinations to overcome drug resistance will be discussed.
癌细胞的化疗耐药性是癌症治疗中的一个主要问题。了解癌细胞可能的死亡方式或对癌症药物的耐药机制对于提供某些策略以克服肿瘤对治疗的耐药性至关重要。紫杉醇是一种化疗药物,通过诱导细胞周期阻滞和有丝分裂灾难来抑制癌细胞的增殖。然而,如今人们已经清楚地认识到,紫杉醇可以在癌症中诱导多种细胞死亡。除了在有丝分裂过程中发生的有丝分裂灾难诱导外,紫杉醇已被证明可以诱导几种促凋亡介质的表达。它还可以调节抗凋亡介质的活性。然而,某些细胞杀伤机制,如衰老和自噬,可以增加对紫杉醇的耐药性。本综述重点讨论了紫杉醇治疗后细胞死亡的机制,包括细胞凋亡、有丝分裂灾难、衰老、自噬细胞死亡、细胞焦亡等。此外,还将讨论由于暴露于紫杉醇而产生的细胞死亡耐药机制以及联合使用以克服耐药性的机制。