Investigation of uniform sized multicellular spheroids raised by microwell arrays after the combined treatment of electr
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Investigation of uniform sized multicellular spheroids raised by microwell arrays after the combined treatment of electric field and anti-cancer drug Kin Fong Lei 1,2
&
Wun-Wu Ji 1 & Andrew Goh 1 & Chun-Hao Huang 3 & Ming-Yih Lee 1,4
# Springer Science+Business Media, LLC, part of Springer Nature 2019
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. Keywords Multicellular spheroids . Microwell arrays . Electric field therapy . Cell apoptosis
1 Introduction In recent years, in vitro investigation of cellular drug response using three dimensional (3D) culture systems are recognized to achieve high predictive cancer chemotherapeutic efficacy Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10544-019-0442-5) contains supplementary material, which is available to authorized users. * Kin Fong Lei [email protected] * Ming-Yih Lee [email protected] 1
Graduate Institute of Biomedical Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan
2
Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, Taiwan
3
PhD Program in Biomedical Engineering, College of Engineering, Chang Gung University, Taoyuan, Taiwan
4
Department of Cardiology, Chang Gung Memorial Hospital, Linkou, Taiwan
(Perche and Torchilin 2012). Especially for the development of new treatment, high physiologically relevant culture models are essential for understanding the tumor responses and mechanisms. Multicellular spheroid model is one of the 3D culture systems and more closely mimics the native microenvironment compared to conventional monolayer culture systems (Sutherland 1988; Dubessy et al. 2000). Multicellular spheroids consist of proliferating cells located in the spheroid surface and quiescent cells located in the
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