Human Mesenchymal Stem Cells Are Resistant to Paclitaxel by Adopting a Non-Proliferative Fibroblastic State

被引:38
作者
Bosco, Dale B. [1 ]
Kenworthy, Rachael [2 ]
Zorio, Diego A. R. [2 ]
Sang, Qing-Xiang Amy [1 ,2 ]
机构
[1] Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA
[2] Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA
来源
PLOS ONE | 2015年 / 10卷 / 06期
关键词
TUMOR-ASSOCIATED FIBROBLASTS; 1ST TOTAL-SYNTHESIS; HUMAN BONE-MARROW; STROMAL CELLS; MULTIDRUG-RESISTANCE; ANTITUMOR-ACTIVITY; DRUG-RESISTANCE; CANCER; CHEMOTHERAPY; SURVIVAL;
D O I
10.1371/journal.pone.0128511
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Human mesenchymal stem cell (hMSC) resistance to the apoptotic effects of chemotherapeutic drugs has been of major interest, as these cells can confer this resistance to tumor microenvironments. However, the effects of internalized chemotherapeutics upon hMSCs remain largely unexplored. In this study, cellular viability and proliferation assays, combined with different biochemical approaches, were used to investigate the effects of Paclitaxel exposure upon hMSCs. Our results indicate that hMSCs are highly resistant to the cytotoxic effects of Paclitaxel treatment, even though there was no detectable expression of the efflux pump P-glycoprotein, the usual means by which a cell resists Paclitaxel treatment. Moreover, Paclitaxel treatment induces hMSCs to adopt a non-proliferative fibroblastic state, as evidenced by changes to morphology, cellular markers, and a reduction in differentiation potential that is not directly coupled to the cytoskeletal effects of Paclitaxel. Taken together, our results show that Paclitaxel treatment does not induce apoptosis in hMSCs, but does induce quiescence and phenotypic changes.
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页数:14
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