Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5827892 | European Journal of Pharmacology | 2014 | 8 Pages |
Abstract
The overexpression of P-glycoprotein (P-gp) causes resistance to chemotherapy in human ovarian cancer. However, the underlying mechanism remains unclear. In the present study, we showed that, at membrane-bound protein level, P-gp was 'shared' between human ovarian cancer cells by the intercellular transfer of microvesicles (MVs). Paclitaxel-resistant human ovarian cancer cells (A2780/PTX) readily formed and released P-gp-containing MVs into the extracellular space compared with the wild-type parental line (A2780/WT). Shedding MVs bound to the chemosensitive A2780/WT cells in a time- and dose-dependent manner, transferring P-gp via the microenvironment. MV-mediated transfer of P-gp led to redistribution of the chemotherapeutic drug adriamycin in recipient cells (A2780/WT), which displayed 5- and 5-fold higher resistance to adriamycin and paclitaxel, respectively. Thus, these findings demonstrate a new mechanism of drug-resistance acquisition via MVs.
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Authors
Fang-fang Zhang, Yi-fei Zhu, Qian-nan Zhao, Dan-tong Yang, Ye-ping Dong, Li Jiang, Wei-xing Xing, Xi-yuan Li, Hui Xing, Mei Shi, Yun Chen, Iain C. Bruce, Jian Jin, Xin Ma,