title: Characterization of Dynamic Behaviour of MCF7 and MCF10A Cells in Ultrasonic Field Using Modal and Harmonic Analyses.
abstract: Treatment options specifically targeting tumour cells are urgently needed in order to reduce the side effects accompanied by chemo- or radiotherapy. Differences in subcellular structure between tumour and normal cells determine their specific elasticity. These structural differences can be utilised by low-frequency ultrasound in order to specifically induce cytotoxicity of tumour cells. For further evaluation, we combined in silico FEM (finite element method) analyses and in vitro assays to bolster the significance of low-frequency ultrasound for tumour treatment. FEM simulations were able to calculate the first resonance frequency of MCF7 breast tumour cells at 21 kHz in contrast to 34 kHz for the MCF10A normal breast cells, which was due to the higher elasticity and larger size of MCF7 cells. For experimental validation of the in silico-determined resonance frequencies, equipment for ultrasonic irradiation with distinct frequencies was constructed. Differences for both cell lines in their response to low-frequent ultrasonic treatment were corroborated in 2D and in 3D cell culture assays. Treatment with ~ 24.5 kHz induced the death of MCF7 cells and MDA-MB-231 metastases cells possessing a similar elasticity; frequencies of > 29 kHz resulted in cytotoxicity of MCF10A. Fractionated treatments by ultrasonic irradiation of suspension myeloid HL60 cells resulted in a significant decrease of viable cells, mostly significant after threefold irradiation in intervals of 3 h. Most importantly in regard to a clinical application, combined ultrasonic treatment and chemotherapy with paclitaxel showed a significantly increased killing of MCF7 cells compared to both monotherapies. In summary, we were able to determine for the first time for different tumour cell lines a specific frequency of low-intensity ultrasound for induction of cell ablation. The cytotoxic effect of ultrasonic irradiation could be increased by either fractionated treatment or in combination with chemotherapy. Thus, our results will open new perspectives in tumour treatment.
authors.affiliation: ASD Advanced Simulation & Design GmbH, Rostock, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Geltmeier
authors.affiliation: Center for Medical Research, Medical University Graz, Graz, Austria.
authors.forename: Beate
authors.initials: B
authors.lastname: Rinner
authors.affiliation: Mechatronic AG, Darmstadt, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Bade
authors.affiliation: Center for Medical Research, Medical University Graz, Graz, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Meditz
authors.affiliation: Oncowave Medical AG, Darmstadt, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Witt
authors.affiliation: Oncowave Medical AG, Darmstadt, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Bicker
authors.affiliation: ASD Advanced Simulation & Design GmbH, Rostock, Germany.
authors.forename: Catrin
authors.initials: C
authors.lastname: Bludszuweit-Philipp
authors.affiliation: Oncowave Medical AG, Darmstadt, Germany; Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Maier
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001253:Astrocytes; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology* / Q000628:therapy; D002460:Cell Line; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004548:Elasticity; D005260:Female; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D061986:MCF-7 Cells; D008954:Models, Biological; D017239:Paclitaxel / Q000494:pharmacology; D014464:Ultrasonic Therapy; D000069453:Ultrasonic Waves
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel