Investigation of uniform sized multicellular spheroids raised by microwell arrays after the combined treatment of electric field and anti-cancer drug

Abstract

Nowadays, cancer disease is continuously identified as the leading cause of mortality worldwide. Cancer chemotherapeutic agents have been continuously developing to achieve high curative effectiveness and low side effects. However, solid tumors present the properties of low drug penetration and resistance of quiescent cells. Radiation therapy is concurrently given in some cases; but it induces different levels of adverse effects. In the current work, uniform sized multicellular spheroids were raised by microwell arrays to mimic the architecture of solid tumors. Investigation of the response of the spheroids was conducted after the treatment of alternating electric field. The result showed that the electric field could induce early apoptosis by disturbing cell membrane. Moreover, combined treatment of electric field and anti-cancer drug was applied to the spheroids. The electric field synergistically enhanced the treatment efficacy because the anti-cancer drug could permeate through the disrupted cell membrane. Significant improvement of late apoptosis was shown by the combined treatment. Because the electric field treatment induces limited side effect to the patient, lower dosage of anti-cancer drug may be applied to the patients for achieving curative effectiveness.

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Acknowledgements

This work was supported by Chang Gung Memorial Hospital, Linkou, Taiwan (project no. CMRPD2H0022 and BMRPC05).

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Correspondence to Kin Fong Lei or Ming-Yih Lee.

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Lei, K.F., Ji, WW., Goh, A. et al. Investigation of uniform sized multicellular spheroids raised by microwell arrays after the combined treatment of electric field and anti-cancer drug. Biomed Microdevices 21, 94 (2019). https://doi.org/10.1007/s10544-019-0442-5

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Keywords

  • Multicellular spheroids
  • Microwell arrays
  • Electric field therapy
  • Cell apoptosis