细胞衰老与癌症治疗

doi:10.13865/j.cnki.cjbmb.2019.11.1285

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摘要细胞衰老是生物界普遍存在的现象。肿瘤细胞是一类摆脱细胞周期束缚，突破Hayflick界限，能够无限增殖而不衰老的细胞。癌症是一种与细胞衰老密切相关的疾病。从进化的角度来看，衰老对于生物体是有益的，可以导致细胞不可逆的周期阻滞，被认为是一种自主的肿瘤抑制机制。在恶性增殖的癌细胞中，在胞外及胞内多种刺激下，如端粒缩短、DNA损伤、氧化应激以及化疗药物的处理等，都会出现细胞周期阻滞，生长迟缓等细胞衰老现象。诱导肿瘤细胞衰老也被认为是一种治疗癌症的有效手段。衰老细胞可以向胞外分泌数十种因子，维持细胞自身衰老表型，并影响周围细胞的生长，这种特性被称为衰老相关的分泌表型(SASP)。本文详细综述细胞衰老的形态学特征与分子标记物及检测方法，细胞衰老的信号调控通路（p53-p21，p16-pRB和PTEN-p27），以及细胞衰老与恶性肿瘤发生发展的关系等。尤其是应激压力诱导下的细胞衰老在癌症治疗中的潜在作用，并进一步讨论当下流行的促衰老癌症治疗的靶点与药物以及存在的问题，以期为今后的研究提供新思路和新方向。

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	崔晓东
	邹娇娇
	王转花

关键词 ：细胞衰老, 衰老相关的分泌表型, 癌症治疗, 促衰老治疗, 药物靶点

Abstract：Cell senescence is a ubiquitous phenomenon in biology. Tumor cells are a kind of cells that can proliferate with impunity and break through the Hayflick limit, and cancer is also considered as a disease related to cell senescence. From an evolutionary perspective, senescence is beneficial to organisms and can lead to irreversible cell cycle arrest, which is considered to be an autonomous tumor suppression mechanism. In malignant proliferating cancer cells, the cell senescence can be triggered by a variety of cell-intrinsic and extrinsic stimuli, including telomere shortening, DNA damage, oxidative stress and exposure to chemotherapeutic agents. Senescent cells can secrete dozen of factors to maintain their own senescence phenotype and affect the growth of surrounding cells. This characteristic is called senescence-associated secretory phenotype (SASP). The induction of senescence in cancer cells is considered to be an emerging means for cancer therapy. This paper reviews the morphological features, molecular markers and detection methods of cell senescence, signal transduction pathways (p53-p21, p16-pRB and PTEN-p27), as well as the relationship between cell senescence and tumorigenesis. Meanwhile we offer an extensive description of current potential pharmacological interventions for pro-senescence therapy for cancer. This article lays a foundation for further elucidating new ideas and new directions for future research.

Key words： cellular senescence senescence-associated secretory phenotype(SASP) cancer therapy pro-senescence therapy drug targets

收稿日期: 2019-07-10 出版日期: 2020-03-06

PACS:

Q26

基金资助:国家自然科学基金项目（No. 31300653）；山西省应用基础研究计划项目（No.201801D121192）和山西省高等学校科技创新项目（No. 201802020）

通讯作者: 王转花 E-mail: zhwang@sxu.edu.cn

引用本文:

崔晓东, 邹娇娇, 王转花. 细胞衰老与癌症治疗[J]. 中国生物化学与分子生物学报, 2020, 36(2): 119-126.
CUI Xiao-Dong, ZOU Jiao-Jiao, WANG Zhuan-Hua. Cell Senescence and Cancer Therapy. Chinese Journal of Biochemistry and Molecular Biol, 2020, 36(2): 119-126.

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http://cjbmb.bjmu.edu.cn/CN/10.13865/j.cnki.cjbmb.2019.11.1285 或 http://cjbmb.bjmu.edu.cn/CN/Y2020/V36/I2/119

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