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Suspension State Promotes Drug Resistance of Breast Tumor Cells by Inducing ABCC3 Overexpression

Mechanical microenvironment plays a critical role in cancer drug resistance and this study supposed that suspension state might be involved in drug resistance of breast tumor cells. The viability of cell was detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tet...

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Published in:Applied biochemistry and biotechnology 2020-02, Vol.190 (2), p.410-422
Main Authors: Wang, Ya, Zhang, Xiaomei, Zhao, Boyuan, Xu, Zhiling, Lv, Yonggang
Format: Article
Language:English
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Summary:Mechanical microenvironment plays a critical role in cancer drug resistance and this study supposed that suspension state might be involved in drug resistance of breast tumor cells. The viability of cell was detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Cell cycle and apoptosis were detected by flow cytometry. Gene and protein were tested by RT-qPCR and Western blot, respectively. Drug resistance of MDA-MB-231 cells cultured for 72 h under suspension state was significantly increased. Suspension state was found to induce the overexpression of adenosine triphosphate–binding cassette subfamily C member 3 (ABCC3) in MDA-MB-231 cells. Silencing of ABCC3 significantly decreased drug resistance of suspension MDA-MB-231 cells. Moreover, suspension state was able to increase lamin A/C accumulation in MDA-MB-231 cells and lamin A/C regulated the expression of ABCC3. Moreover, lamin A/C knockdown also decreased drug resistance of suspension MDA-MB-231 cells, but the effect on drug resistance was less than that of ABCC3 knockdown. Suspension state plays a vital role in promoting drug resistance of MDA-MB-231 cells by inducing ABCC3 overexpression, and lamin A/C accumulation is associated with this process.
ISSN:0273-2289
1559-0291
DOI:10.1007/s12010-019-03084-0