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Characterization of Dynamic Behaviour of MCF7 and MCF10A Cells in Ultrasonic Field Using Modal and Harmonic Analyses.

Geltmeier A, Rinner B, Bade D, Meditz K, Witt R, Bicker U, Bludszuweit-Philipp C, Maier P - PLoS ONE (2015)

Bottom Line: 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.The cytotoxic effect of ultrasonic irradiation could be increased by either fractionated treatment or in combination with chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: ASD Advanced Simulation & Design GmbH, Rostock, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Harmonic vibration analysis of (A) MCF7 and (B) MCF10A cells (minimal sizes for both cell types) with external hydrostatic pressure in a frequency range of 20 kHz up to 60 kHz showing the displacement amplitudes.The red horizontal lines depict the maximum cell size which allows the amplitudes with the cell dimension to be compared.
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pone.0134999.g003: Harmonic vibration analysis of (A) MCF7 and (B) MCF10A cells (minimal sizes for both cell types) with external hydrostatic pressure in a frequency range of 20 kHz up to 60 kHz showing the displacement amplitudes.The red horizontal lines depict the maximum cell size which allows the amplitudes with the cell dimension to be compared.

Mentions: As a result of a harmonic analysis, an amplitude frequency response can be determined that delivers resonance frequencies and the corresponding amplitudes. For the analysed cell models of minimum, mean, and maximum cell dimensions of both cell types, the range of excitation frequency was defined from the initial natural frequency up to 60 kHz. Cell type and dimension showed a great influence on the amplitude frequency response. A typical amplitude frequency response diagram is shown in Fig 3 for a MCF7 cells and MCF10A cells of minimum dimension (see Table 1). The depicted amplitude’s frequency response showed significant peaks at those frequencies at which oscillation forms were excited by the ultrasonic pressure. The first peak for MCF7 cells rose at 21 kHz in contrast to 34 kHz for MCF10A cells. Especially this first maximum resonance amplitude of MCF7 cells amounted to more than three times the maximum cell length, indicating huge stress on cellular integrity. The first resonance frequencies of MCF7 cells of mean dimension were also significantly lower than those of MCF10A cells. In contrast, the differences between the resonance frequencies and the amplitudes were smaller for the maximum cell dimensions of both cell lines (data not shown).


Characterization of Dynamic Behaviour of MCF7 and MCF10A Cells in Ultrasonic Field Using Modal and Harmonic Analyses.

Geltmeier A, Rinner B, Bade D, Meditz K, Witt R, Bicker U, Bludszuweit-Philipp C, Maier P - PLoS ONE (2015)

Harmonic vibration analysis of (A) MCF7 and (B) MCF10A cells (minimal sizes for both cell types) with external hydrostatic pressure in a frequency range of 20 kHz up to 60 kHz showing the displacement amplitudes.The red horizontal lines depict the maximum cell size which allows the amplitudes with the cell dimension to be compared.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524665&req=5

pone.0134999.g003: Harmonic vibration analysis of (A) MCF7 and (B) MCF10A cells (minimal sizes for both cell types) with external hydrostatic pressure in a frequency range of 20 kHz up to 60 kHz showing the displacement amplitudes.The red horizontal lines depict the maximum cell size which allows the amplitudes with the cell dimension to be compared.
Mentions: As a result of a harmonic analysis, an amplitude frequency response can be determined that delivers resonance frequencies and the corresponding amplitudes. For the analysed cell models of minimum, mean, and maximum cell dimensions of both cell types, the range of excitation frequency was defined from the initial natural frequency up to 60 kHz. Cell type and dimension showed a great influence on the amplitude frequency response. A typical amplitude frequency response diagram is shown in Fig 3 for a MCF7 cells and MCF10A cells of minimum dimension (see Table 1). The depicted amplitude’s frequency response showed significant peaks at those frequencies at which oscillation forms were excited by the ultrasonic pressure. The first peak for MCF7 cells rose at 21 kHz in contrast to 34 kHz for MCF10A cells. Especially this first maximum resonance amplitude of MCF7 cells amounted to more than three times the maximum cell length, indicating huge stress on cellular integrity. The first resonance frequencies of MCF7 cells of mean dimension were also significantly lower than those of MCF10A cells. In contrast, the differences between the resonance frequencies and the amplitudes were smaller for the maximum cell dimensions of both cell lines (data not shown).

Bottom Line: 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.The cytotoxic effect of ultrasonic irradiation could be increased by either fractionated treatment or in combination with chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: ASD Advanced Simulation & Design GmbH, Rostock, Germany.

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.

No MeSH data available.


Related in: MedlinePlus