Microparticles induce multifactorial resistance through oncogenic pathways independently of cancer cell type.
Bottom Line: By co-culturing MP derived from MDR-positive cells with recipient cells, we showed that sensitive cells accumulated Pgp, IAP proteins and mRNA.In addition, MP promoted microRNA transfer and NFκB and Yb-1 activation.Therefore, our results indicate that MP can induce a multifactorial phenotype in sensitive cancer cells.
Affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.Show MeSH
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Mentions: To evaluate whether acquiring Pgp expression and enhancement of survivin, XIAP and cIAP1 expression could, in fact, induce the MDR phenotype in recipient cells, we tested Pgp efflux pump activity and apoptosis inhibition using chemotherapeutic agents. As shown in Figure4, A549 and MCF7 recipient cells acquired functional Pgp with little efflux pump activity after co-culturing with an MDR-positive donor cell line (MFI = 1.3 and 1.4, respectively). To analyze apoptosis, A549 and MCF7 cell lines were treated with cisplatin and paclitaxel, respectively, for 24 h after co-culturing with a Pgp-positive donor cell line. The apoptosis index of A549 cells was reduced from 40% to approximately 6% after co-culture with MP (Fig.4b). MCF7 cells showed a similar reduction, from 30% to approximately 14% (Fig.4c). These results show that MDR cell-derived MP can induce a drug resistant phenotype in sensitive cell lines.
Affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.