Diversity of the Senescence Phenotype of Cancer Cells Treated with Chemotherapeutic Agents
Diversity of the Senescence Phenotype of Cancer Cells Treated with Chemotherapeutic Agents
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DOI：
10.3390/cells8121501
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发表时间：
2019-12-01
期刊：
影响因子：
6
通讯作者：
Sikora, Ewa
中科院分区：
文献类型：
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作者：
Bojko, Agnieszka;Czarnecka-Herok, Joanna;Sikora, Ewa
人们已经认识到，癌细胞能够在临床使用的化疗药物的作用下发生衰老。此外，近年来提供的证据表明，一些药物可以选择性地去除衰老细胞。因此，正确识别和描述衰老细胞是至关重要的，尤其是在癌症方面。阿霉素、伊立替康、甲氨蝶呤、5-氟尿嘧啶、奥沙利铂或紫杉醇处理后，A549、SH-SY-5Y、HCT116、MDA-MB-231和MCF-7等多种癌细胞均发生衰老。经化疗药物治疗后，p21蛋白表达上调，细胞增殖受阻，且无细胞毒性。与常用衰老标志物(即形态、SA-β-半乳糖苷酶、粒度、分泌表型和双链DNA损伤水平)的比较分析表明，不同化疗药物的反应存在很大差异。阿霉素、伊立替康和甲氨蝶呤的促衰老作用最强，紫杉醇次之，奥沙利铂和5-氟尿嘧啶无促衰作用。此外，还观察到不同癌细胞对衰老的敏感性不同。一项旨在发现所应用的衰老标记之间的任何关系的统计分析没有显示出明显的相关性。此外，SA-β-Gal活性的增加与p21的表达相结合并不是一个明确的衰老标志。这表明，考虑到它们各自的局限性，需要同时分析多个标记。
It is acknowledged that cancer cells are able to undergo senescence in response to clinically used chemotherapeutics. Moreover, recent years have provided evidence that some drugs can selectively remove senescent cells. Therefore, it is essential to properly identify and characterize senescent cells, especially when it comes to cancer. Senescence was induced in various cancer cell lines (A549, SH-SY-5Y, HCT116, MDA-MB-231, and MCF-7) following treatment with doxorubicin, irinotecan, methotrexate, 5-fluorouracil, oxaliplatin, or paclitaxel. Treatment with tested chemotherapeutics resulted in upregulation of p21 and proliferation arrest without cytotoxicity. A comparative analysis with the use of common senescence markers (i.e., morphology, SA-beta-galactosidase, granularity, secretory phenotype, and the level of double-stranded DNA damage) revealed a large diversity in response to the chemotherapeutics used. The strongest senescence inducers were doxorubicin, irinotecan, and methotrexate; paclitaxel had an intermediate effect and oxaliplatin and 5-fluorouracil did not induce senescence. In addition, different susceptibility of cancer cells to senescence was observed. A statistical analysis aimed at finding any relationship between the senescence markers applied did not show clear correlations. Moreover, increased SA-beta-gal activity coupled with p21 expression proved not to be an unequivocal senescence marker. This points to a need to simultaneously analyze multiple markers, given their individual limitations.