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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

Increased death of U-87 MG, U251 MG, and MDA-MB-361 cells after irradiation with an ultrasonic frequency of 29 kHz.Normal rat astrocytes (CTX TNA2) were not affected by irradiation with 29 kHz. Results represent the means of data from four to six independent experiments; the error bars represent the standard errors; p-values were calculated by the two-sided, paired Student’s t-test with * p<0.05, ** p<0.01, *** p<0.001.
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pone.0134999.g006: Increased death of U-87 MG, U251 MG, and MDA-MB-361 cells after irradiation with an ultrasonic frequency of 29 kHz.Normal rat astrocytes (CTX TNA2) were not affected by irradiation with 29 kHz. Results represent the means of data from four to six independent experiments; the error bars represent the standard errors; p-values were calculated by the two-sided, paired Student’s t-test with * p<0.05, ** p<0.01, *** p<0.001.

Mentions: In order to broaden our findings to other cancer cell lines, we treated two glioblastoma cells lines, U-87 MG and U-251 MG, the brain metastasis cell line MDA-MB-361, and the rat astrocyte line CTX TNA2, as normal tissue cells (a human analogue has not been made commercially available) with seven different frequencies in the range of 22.9 kHz up to 51.2 kHz (data not shown). The use of 29.4 kHz resulted in a significant increase of cytotoxicity of all three tumour cell lines (Fig 6). In contrast, normal astrocytes showed no increase in cell death at this frequency (Fig 6) as well as at the other six frequencies (data not shown). Thus, we were able to show a tumour-specific ultrasonic frequency for induction of cell death.


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)

Increased death of U-87 MG, U251 MG, and MDA-MB-361 cells after irradiation with an ultrasonic frequency of 29 kHz.Normal rat astrocytes (CTX TNA2) were not affected by irradiation with 29 kHz. Results represent the means of data from four to six independent experiments; the error bars represent the standard errors; p-values were calculated by the two-sided, paired Student’s t-test with * p<0.05, ** p<0.01, *** p<0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0134999.g006: Increased death of U-87 MG, U251 MG, and MDA-MB-361 cells after irradiation with an ultrasonic frequency of 29 kHz.Normal rat astrocytes (CTX TNA2) were not affected by irradiation with 29 kHz. Results represent the means of data from four to six independent experiments; the error bars represent the standard errors; p-values were calculated by the two-sided, paired Student’s t-test with * p<0.05, ** p<0.01, *** p<0.001.
Mentions: In order to broaden our findings to other cancer cell lines, we treated two glioblastoma cells lines, U-87 MG and U-251 MG, the brain metastasis cell line MDA-MB-361, and the rat astrocyte line CTX TNA2, as normal tissue cells (a human analogue has not been made commercially available) with seven different frequencies in the range of 22.9 kHz up to 51.2 kHz (data not shown). The use of 29.4 kHz resulted in a significant increase of cytotoxicity of all three tumour cell lines (Fig 6). In contrast, normal astrocytes showed no increase in cell death at this frequency (Fig 6) as well as at the other six frequencies (data not shown). Thus, we were able to show a tumour-specific ultrasonic frequency for induction of cell death.

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