TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transportersReportar como inadecuado




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BMC Cancer

, 10:229

First Online: 23 May 2010Received: 28 December 2009Accepted: 23 May 2010DOI: 10.1186-1471-2407-10-229

Cite this article as: Schneiderman, R.S., Shmueli, E., Kirson, E.D. et al. BMC Cancer 2010 10: 229. doi:10.1186-1471-2407-10-229

Abstract

BackgroundExposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields - TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin.

MethodsThree pairs of wild type-MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative C11 of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line Emt; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7-Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231-Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs.

ResultsTTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields-drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells.

ConclusionsThe results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors.

List of abbreviationsMDRmultidrug resistance

TTFieldstumor treating electric fields

DRIdose reduction index

WTwild type.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-229 contains supplementary material, which is available to authorized users.

Rosa S Schneiderman and Yoram Palti contributed equally to this work.

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Autor: Rosa S Schneiderman - Esther Shmueli - Eilon D Kirson - Yoram Palti

Fuente: https://link.springer.com/







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