A chemotherapy-associated senescence bystander effect in breast cancer cells
A chemotherapy-associated senescence bystander effect in breast cancer cells
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DOI：
10.4161/cbt.7.6.5861
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发表时间：
2008-06-01
影响因子：
3.6
通讯作者：
Elmore, Lynne
中科院分区：
文献类型：
--
作者：
Di, Xu;Bright, Andrew Taylor;Elmore, Lynne
旁观者效应通常是指未直接接受化疗或放疗的细胞死亡、生长改变或损伤。源自实体瘤的癌细胞在化疗药物的作用下很容易发生衰老，这促使我们测试衰老旁观者效应的存在。 MCF-7 乳腺癌细胞急剧暴露于阿霉素以引发衰老。初始MCF-7细胞在来自衰老乳腺癌细胞的条件培养基中培养时，尽管受到有丝分裂刺激，但生长仍停滞，并表现出SA-β-半乳糖苷酶活性、细胞尺寸增大和p21（WAF1）蛋白稳定上调，共同表明衰老状态。相比之下，HCT-116结肠癌细胞也响应急性AdR而经历p53介导的衰老，当与来自衰老HCT-116细胞的条件培养基一起培养时，不会经历生长抑制或衰老。交互实验表明，初始 HCT-116 细胞与 MCF-7 细胞一样，容易受到乳腺癌衍生介质的生长抑制作用，该作用与条件培养基中的残留药物无关。我们的研究揭示了阿霉素的一种新作用，这可能有助于其有效的抗乳腺癌活性，并导致发现利用衰老旁观者效应的其他治疗靶点。
A bystander effect typically refers to the death, altered growth or damage of cells that have not directly received chemotherapy or irradiation. Cancer cells derived from solid tumors readily undergo senescence in response to chemotherapeutic agents, prompting us to test for the existence of a senescence bystander effect. MCF-7 breast cancer cells were acutely exposed to Adriamycin to trigger senescence. Naive MCF-7 cells, when cultured in conditioned media from senescent breast cancer cells, growth arrested despite mitogenic stimulation and exhibited SA-beta-galactosidase activity, an enlarged cell size and stable upregulation of p21(WAF1) protein, collectively indicating a senescent state. In contrast, HCT-116 colon cancer cells, which also undergo p53-mediated senescence in response to acute AdR, did not undergo growth inhibition or senescence when cultured with conditioned media from senescent HCT-116 cells. Reciprocal experiments indicated that naive HCT-116 cells, like MCF-7 cells, are susceptible to the growth inhibitory effects of a breast cancer-derived mediator, which is independent of residual drug in conditioned media. Our study reveals a novel action of Adriamycin, which may contribute to its potent anti-breast cancer activity and lead to the discovery of additional therapeutic targets for the exploitation of a senescence bystander effect.