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The induced protoporphyrin Ⅸ the mediated sonodynamic therapy breast cancer MDA-MB-231 cells and its mechanism

Author: ZhaoPing
Tutor: LiuQuanHong
School: Shaanxi Normal University
Course: Cell Biology
Keywords: Sonodynamic therapy MDA-MB-231 cells Apoptosis p38MAPK protein
CLC: R737.9
Type: Master's thesis
Year: 2011
Downloads: 28
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Abstract

Breast cancer is a serious threat to human health and the life of one of malignant tumors, showed an increasing trend in morbidity and mortality. To date, the clinical treatment have yet to find a non-invasive, safe and satisfactory effect a cure, therefore, the prevention and treatment of breast cancer research is even more urgent. In recent years, there has been some physical therapy for the treatment of cancer, the ultrasound activated sound dynamics of sonosensitizer antitumor therapy (Sonodynamic therapy, SDT) is one of them. The therapy uses ultrasonic strong penetrating human tissue, especially focused ultrasound for non-invasive acoustic energy gathered in the deep tumor site, and activate the sonosensitizer (such as the porphyrin sonosensitizer) to produce the anti-tumor effect . At home and abroad has carried out a series of studies on SDT anti-tumor, showed better clinical cancer treatment prospects. In this thesis, relying on the funding of the Special Research Fund of the Ministry of Education Doctoral Program of Higher protoporphyrin Ⅸ as sonosensitizer with a frequency of 1.1 MHz ultrasound, MDA-MB human breast cancer clinical research has important reference value -231 cells as an experimental model, initially explored the role of p38 MAPK pathway activation the SDT system induced protoporphyrin Ⅸ mediated breast cancer MDA-MB-231 cells apoptosis. Papers protoporphyrin Ⅸ metabolism and positioning in the MDA-MB-231 cells were analyzed; protoporphyrin Ⅸ different concentrations and different ultrasonic power cell viability was measured;, and the generation of reactive oxygen species, mitochondrial membrane potential changes in apoptosis-related proteins and p38 MAPK protein expression detection and analysis, and to provide a theoretical basis for for SDT anti-breast cancer clinical research. The research results are as follows: 1. Protoporphyrin Ⅸ content in MDA-MB-231 cells was a dynamic process of change, when the concentrations of 0.5, 1 and 10μM and the cells were incubated for 2 h, the cells of the original porphyrin Ⅸ enrichment reached the maximum, and then gradually decreased with the incubation time, so the selected 2H best ultrasonic irradiation time. Ultrasound frequency of 1.1 MHz of pure ultrasound on the degree of cell damage with increasing power and enhanced performance for a simple ultrasound intensity when 4W/cm2, greater impact on cell viability, cell survival rate was 44.6%; strength 2W/cm2 no significant activity had no effect on cells, cell survival rate was 92.9%, the paper select ultrasonic power thresholds 3W/cm2 as a follow-up mechanism to explore. 3. Of pure protoporphyrin IX cell viability with the increase in the concentration of protoporphyrin Ⅸ gradually reduced the concentration of protoporphyrin Ⅸ elected 1μM, close to the critical threshold of cell damage. The 1μM The protoporphyrin IX binding 3W/cm2 ultrasound combined effects of MDA-MB-231 cells, exhibit obvious damage to synergistic effects, compared with 3W/cm2 simple ultrasound and 1μM pure protoporphyrin IX, a significant difference . 4.1μM protoporphyrin Ⅸ with 3W/cm2 of ultrasound combined effects of MDA-MB-231 cells, and found that cell survival and processed within 24h after delay no obvious correlation: the ultrasonic plus protoporphyrin Ⅸ group of cells in treated 0h, 6h, 12h and 24h. derived cell viability, and found no significant difference in cell viability different time points. 5.1μM of protoporphyrin Ⅸ the United 3W/cm2 ultrasound can induce apoptosis in MDA-MB-231 cells, and Western blot detection cell death accompanied by apoptosis-related protein caspase-9, caspase-3 and PARP activation. Laser confocal microscope to protoporphyrin Ⅸ MDA-MB-231 cells mitochondria colocalization; flow cytometry results show SDT processing cells can produce reactive oxygen and reactive oxygen species on cell proliferation inhibition lowering of the inner mitochondrial membrane permeability changes and membrane potential enhancement; inhibition of reactive oxygen species can weaken the SDT-induced activation of Caspase-3, and to a certain extent, to prevent the occurrence of apoptosis, reactive oxygen species may promote cell withered death, reactive oxygen species may be upstream factors SDT-induced apoptosis of MDA-MB-231 cells. 7 Western blot detection of p38 MAPK protein expression levels were significantly higher, indicating that its activation of protoporphyrin IX-SDT-induced apoptosis of MDA-MB-231, inhibited activation can be partially weakened cell death effects and reduce apoptosis related protein expression levels. Join the active oxygen inhibitors significantly reduce the SDT-induced p38 MAPK protein expression levels prove protoporphyrin IX-SDT mechanism of MDA-MB-231 cell damage, reactive oxygen species-induced apoptosis and p38 MAPK protein activation closely linked.

The induced protoporphyrin Ⅸ the mediated sonodynamic therapy breast cancer MDA-MB-231 cells and its mechanism

Abstract

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