TGFβ信号调控阿霉素诱导的衰老肿瘤细胞表达SA-β-gal  

TGFβ Signaling Regulates SA-β-gal Expression in Doxorubicin-induced Senescent Tumor Cells

作　　者：许东旭[1,2] 张力[1,2] 杨兆娟[1,2] 夏苏华[1,2] 刘永忠[1,2] 

机构地区：[1]上海交通大学医学院附属仁济医院 [2]上海市肿瘤研究所癌基因及相关基因国家重点实验室,上海200240

出　　处：《现代生物医学进展》2013年第10期1801-1806,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81201542)

摘　　要：目的:细胞衰老是维持机体稳态的一种重要机制,表达SA-β-gal被认为是衰老细胞的一种特异性的标志,但有研究表明在衰老细胞中SA-β-gal染色阳性只是衰老细胞的溶酶体变大的结果,为了探究SA-β-gal的表达与细胞衰老之间的具体关系,我们验证了参与调节衰老细胞表达SA-β-gal的信号通路及SA-β-gal的表达情况是否会对细胞衰老的过程产生影响。方法:肿瘤细胞用低剂量的阿霉素处理24小时后,再分别给予不同的小分子抑制剂继续作用4天,观察SA-β-gal染色阳性的细胞数目及SA-β-gal表达与否对于衰老细胞在分泌细胞因子、生长阻滞等细胞生物学功能上的影响。结果:在阿霉素诱导细胞发生衰老的过程中,TGFβ抑制剂SB431542能够抑制衰老细胞表达SA-β-gal,而SA-β-gal表达的缺失并不影响细胞衰老的其他特征性改变。结论:低剂量的阿霉素作用肿瘤细胞后,细胞会进入衰老的状态。在细胞衰老的过程中,TGFβ受体I的抑制剂SB431542可以抑制衰老细胞表达SA-β-gal,但是SA-β-gal的缺失表达并不影响细胞衰老的过程及衰老细胞的其他特性,如:不可逆的生长阻滞、分泌有活性的细胞因子等。结果表明:SA-β-gal并不能作为衰老细胞的特异性标志。Objective： Cellular senescence is a key mechanism for the homeostasis of an organism.The expression of SA-β-gal is recognized as the specific marker for senescence.But the previous studies showed that SA-β-gal expression in the senescent cells was just caused by enlarged lysosomes.To identify the relationship between SA-β-gal and cellular senescence,we detected the pathways that take part in regulating SA-β-gal expression in senescent cells and the influence of negative SA-β-gal expression to senescence.Methods： Tumor cells were treated with low dose doxorubicin for 24 h,and then cultured in the presence of different small molecule inhibitors for 4 days.The SA-β-gal positive cells were counted and the influence of SA-β-gal expression to the biological functions in senescent cells was detected.Results： During the doxorubicin-induced senescence progression,TGFβ inhibitor SB431542 can inhibit SA-β-gal expression and the absence of SA-β-gal expression don’t disturb other senescence-associated properties.Conclusions： Low dose doxorubicin can induce tumor cells into senescence.During senescence progression,TGF-β receptor I inhibitor SB431542 can inhibit SA-β-gal expression in senescent cells,but cells negative for SA-β-gal expression still have other senescence-associated properties,such as： irreversible growth arrest,secretion of functional factors etc.The results show that SA-β-gal may not be the specific marker for senescence.

关 键 词：衰老相关-β-半乳糖苷酶 转化生长因子β 半乳糖苷酶beta1 

分 类 号：Q255[生物学—细胞生物学] Q28