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Microparticles induce multifactorial resistance through oncogenic pathways independently of cancer cell type.

de Souza PS, Cruz AL, Viola JP, Maia RC - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.

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Multidrug resistance (MDR)-negative cells acquire resistance phenotype after co-culturing with MDR-positive cells. MDR-positive cells transfer a functional Pgp (a) to A549 cells (left panel) and MCF7 cells (right panel). P-glycoprotein (Pgp) activity of A549 (MFI = 1.3) and MCF7 (MFI = 1,4) recipient cells were analyzed by flow cytometry after incubation with rhodamine-123 fluorochrome (Rho-123) with or without cyclosporine A (CsA). The solid gray histogram represents positive activity of Pgp and the hatched black histogram represents cells with Rho-123 (right) or cells alone (left). A549 cells (b) and MCF7 cells (c) were treated with cisplatin and paclitaxel, respectively, for 24 h, and induced cell death was analyzed by flow cytometry using Annexin V and propidium iodide (PI) staining. Cisplatin induced approximately 40% of cell death in A549 cells (middle panel) and only approximately 6% of cell death (right panel) after co-culturing with MDR-positive cells. Untreated cells are represented in the left panel (b). Paclitaxel induced approx. 30% of cell death in MCF7 cells (middle panel) and only approximately 14% of cell death (right panel) in these cells after co-culturing with Pgp-positive cells. Untreated cells are represented in the left panel (c).
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fig04: Multidrug resistance (MDR)-negative cells acquire resistance phenotype after co-culturing with MDR-positive cells. MDR-positive cells transfer a functional Pgp (a) to A549 cells (left panel) and MCF7 cells (right panel). P-glycoprotein (Pgp) activity of A549 (MFI = 1.3) and MCF7 (MFI = 1,4) recipient cells were analyzed by flow cytometry after incubation with rhodamine-123 fluorochrome (Rho-123) with or without cyclosporine A (CsA). The solid gray histogram represents positive activity of Pgp and the hatched black histogram represents cells with Rho-123 (right) or cells alone (left). A549 cells (b) and MCF7 cells (c) were treated with cisplatin and paclitaxel, respectively, for 24 h, and induced cell death was analyzed by flow cytometry using Annexin V and propidium iodide (PI) staining. Cisplatin induced approximately 40% of cell death in A549 cells (middle panel) and only approximately 6% of cell death (right panel) after co-culturing with MDR-positive cells. Untreated cells are represented in the left panel (b). Paclitaxel induced approx. 30% of cell death in MCF7 cells (middle panel) and only approximately 14% of cell death (right panel) in these cells after co-culturing with Pgp-positive cells. Untreated cells are represented in the left panel (c).

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.


Microparticles induce multifactorial resistance through oncogenic pathways independently of cancer cell type.

de Souza PS, Cruz AL, Viola JP, Maia RC - Cancer Sci. (2014)

Multidrug resistance (MDR)-negative cells acquire resistance phenotype after co-culturing with MDR-positive cells. MDR-positive cells transfer a functional Pgp (a) to A549 cells (left panel) and MCF7 cells (right panel). P-glycoprotein (Pgp) activity of A549 (MFI = 1.3) and MCF7 (MFI = 1,4) recipient cells were analyzed by flow cytometry after incubation with rhodamine-123 fluorochrome (Rho-123) with or without cyclosporine A (CsA). The solid gray histogram represents positive activity of Pgp and the hatched black histogram represents cells with Rho-123 (right) or cells alone (left). A549 cells (b) and MCF7 cells (c) were treated with cisplatin and paclitaxel, respectively, for 24 h, and induced cell death was analyzed by flow cytometry using Annexin V and propidium iodide (PI) staining. Cisplatin induced approximately 40% of cell death in A549 cells (middle panel) and only approximately 6% of cell death (right panel) after co-culturing with MDR-positive cells. Untreated cells are represented in the left panel (b). Paclitaxel induced approx. 30% of cell death in MCF7 cells (middle panel) and only approximately 14% of cell death (right panel) in these cells after co-culturing with Pgp-positive cells. Untreated cells are represented in the left panel (c).
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fig04: Multidrug resistance (MDR)-negative cells acquire resistance phenotype after co-culturing with MDR-positive cells. MDR-positive cells transfer a functional Pgp (a) to A549 cells (left panel) and MCF7 cells (right panel). P-glycoprotein (Pgp) activity of A549 (MFI = 1.3) and MCF7 (MFI = 1,4) recipient cells were analyzed by flow cytometry after incubation with rhodamine-123 fluorochrome (Rho-123) with or without cyclosporine A (CsA). The solid gray histogram represents positive activity of Pgp and the hatched black histogram represents cells with Rho-123 (right) or cells alone (left). A549 cells (b) and MCF7 cells (c) were treated with cisplatin and paclitaxel, respectively, for 24 h, and induced cell death was analyzed by flow cytometry using Annexin V and propidium iodide (PI) staining. Cisplatin induced approximately 40% of cell death in A549 cells (middle panel) and only approximately 6% of cell death (right panel) after co-culturing with MDR-positive cells. Untreated cells are represented in the left panel (b). Paclitaxel induced approx. 30% of cell death in MCF7 cells (middle panel) and only approximately 14% of cell death (right panel) in these cells after co-culturing with Pgp-positive cells. Untreated cells are represented in the left panel (c).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Program of Hemato-Oncology Molecular, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.

Show MeSH
Related in: MedlinePlus