腫瘤細(xì)胞衰老及相關(guān)治療的研究進(jìn)展

張瑞新 寧方玲

[摘要]細(xì)胞衰老是一種多效性的細(xì)胞狀態(tài)，貫穿于機(jī)體生理及病理多重環(huán)節(jié)的始末，維持細(xì)胞與組織自身功能及結(jié)構(gòu)的動(dòng)態(tài)平衡。傳統(tǒng)意義上，細(xì)胞衰老以永久性的增殖停滯為特征，以各種治療手段加速腫瘤細(xì)胞衰老成為既往腫瘤治療的一大理論基石，然而，近年來人們對(duì)于細(xì)胞衰老機(jī)制的探索不斷深入，發(fā)現(xiàn)由于腫瘤微環(huán)境中的細(xì)胞衰老現(xiàn)象具有特殊的生物學(xué)特性，一些衰老腫瘤細(xì)胞甚至可以“重啟”細(xì)胞周期，從而實(shí)現(xiàn)“重生”并獲得更高的侵襲能力及治療抵抗性。研究證實(shí)，這種現(xiàn)象與腫瘤治療后復(fù)發(fā)有密切關(guān)聯(lián)。本文將對(duì)腫瘤細(xì)胞衰老的相關(guān)機(jī)制進(jìn)行歸納總結(jié)，并對(duì)其相關(guān)誘導(dǎo)及清除治療的研究進(jìn)展進(jìn)行綜述。

[關(guān)鍵詞]腫瘤;細(xì)胞衰老;衰老誘導(dǎo)治療;細(xì)胞周期

[中圖分類號(hào)] R730.5? [文獻(xiàn)標(biāo)識(shí)碼] A?? [文章編號(hào)]2095-0616（2022）09-0062-04

Study advances in tumor cell senescence and related therapies ZHANG? Ruixin ???NING? Fangling2

1.Binzhou Medical University， Shandong， Binzhou 256603， China;2.Department of Oncology， Binzhou Medical University Hospital， Shandong， Binzhou 256603， China

[Abstract] Cell senescence is a pleiotropic cellular state that runs through the beginning and end of multiple processes of body physiology and pathology， maintaining the dynamic balance of the functions and structures of cells and tissues. Traditionally， cell senescence is characterized by permanent proliferation stagnation， and accelerating tumor cell senescence by various therapeutic means has been a major theoretical cornerstone of tumor therapy in the past. However， in recent years， the exploration on cell senescence mechanisms has been deepened， and it has been found that some senescent tumor cells can even "restart" the cell cycle due to the special biological characteristics of cell senescence in the tumor microenvironment， thus achieving "rebirth" and higher invasion ability and therapeutic resistance. And this phenomenon has been proven to be closely related to tumor recurrence after treatment. This paper summarizes the mechanisms of tumor cell senescence and reviews the study advances in the senescence-inducing and eradication therapy.

[Key words] Tumor; Cell senescence; Senescence-inducing therapy; Cell cycle

“細(xì)胞衰老”（cellular senescence）一詞由 Hayflick 團(tuán)隊(duì)首次提出，他們觀察到正常的二倍體細(xì)胞在有限次數(shù)的分裂后停止增殖，現(xiàn)象類似于機(jī)體衰老，故將其命名為“細(xì)胞衰老”[1]。事實(shí)上，盡管細(xì)胞衰老與機(jī)體衰老存在相關(guān)性，但二者并非對(duì)等關(guān)系。從胚胎發(fā)育到成年期的任何生命階段，細(xì)胞在機(jī)體生長(zhǎng)發(fā)育的任何階段都可以經(jīng)歷衰老，并不受年齡限制。在胚胎發(fā)育階段，細(xì)胞衰老有助于機(jī)體生長(zhǎng)發(fā)育，而成年階段，細(xì)胞衰老可以阻止受損細(xì)胞的繁殖，有助于組織修復(fù)，并起到抑制腫瘤發(fā)生的作用[2]。總之，細(xì)胞衰老是在漫長(zhǎng)的進(jìn)化過程中，細(xì)胞自身演變出一套相對(duì)完善的動(dòng)態(tài)平衡調(diào)控程序。……