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The morbidity and mortality of breast cancer female malignancy in China now ranks first, primary malignant tumors of women's health. Current treatment methods include surgery, radiation therapy, chemotherapy drugs, endocrine therapy and molecular targeted therapy treatment. Breast cancer after initial treatment of the 5-year survival of about 50% to 60%, but still nearly 50% of patients after treatment, recurrence and metastasis. Chemotherapy is the main treatment for breast cancer recurrence and metastasis, but the effect has reached the platform. Combination therapy can improve the efficiency and extend the disease-free survival, but the combination does not significantly prolong overall survival. And chemotherapy to kill tumor cells while not indiscriminately kill normal cells, toxic side effects, the patient unbearable and can not adhere to treatment. Although the importance of endocrine therapy increased to the same height with chemotherapy, radiotherapy, but by the estrogen receptor in breast cancer stars restrictions in estrogen receptor-negative, high metastatic, highly malignant breast cancer stars efficacy and is not obvious. The lack of efficacy of advanced breast cancer treatment, the median survival time is short, the mean survival time of only 18 to 30 months. Therefore, searching for new methods of treatment of breast cancer, is still the hot spot of today's medical research. The SDT (Sonodynamic therapy SDT) developed a tumor in the photodynamic therapy (Photodynamic therapy, PDT) based on the treatment of new ideas, new methods. The SDT will organize the penetrating power of ultrasound instead of the PDT laser to kill tumor cells by tumor tissue on the priority sonosensitizer intake and long retention characteristics, followed by a certain frequency of ultrasonic excitation sonosensitizer. The ultrasonic wave has a strong penetration capability, aggregation and activation of the sound-sensitive drug within the area of ??the tumor tissue, giving rise to a series of biochemical reactions (such as cavitation and produce singlet oxygen) so that the tumor cells to irreversible damage. Red selective focus and ultrasonic penetrating power, and the surrounding normal tissue with less damage, so the anti-tumor effect of the SDT has good application prospects. Sound-power view of the fact that the majority of the photosensitizer, sonodynamic use of photosensitizer said anything sensitizer, but there are two problems: First, the photosensitizer tumor-specific aggregation and disadvantages of normal tissue to clear slow and light side effects, limit the SDT has been approved for clinical use, and therefore need to develop new sonosensitizer; SDT how to further improve the efficacy in combination with other treatment. Photosensitizer chlorin e6 with tumor-specific aggregation, excretion, etc., since most of the photosensitizer sound-power at the same time, we use as sonosensitizer first observed the sound dynamic effects mediated breast cancer cells MDA-MB-231 growth. In recent years, photodynamic therapy combined with chemotherapy treatment of malignant tumors has received increasing attention, Matthew Peterson, Canti G and Kirveliene. Photosensitizer mediated PDT combined with adriamycin treatment of malignant tumors, found that doxorubicin PDT The sensitizing effect of anti-tumor effect, and the effect of timing. The second purpose of this study is observed doxorubicin of Chlorin e6 sonosensitizer SDT inhibition of breast cancer cells MDA-MB-231 growth, aims to explore the doxorubicin chlorin Chlorin e6 SDT whether the sensitizing effect. The first part of chlorin e6-mediated sonodynamic effect on MDA-MB-231 cells as well as the impact of growth of PMNC cells ultrasound and dihydro-porphine e6 alone and combined treatment of MDA-MB-231 cells and normal human peripheral blood mononuclear cells PMNC, and 45 min after using the MTT (MTT) assay for measuring cell growth, fluorescence inverted microscope cell morphology. Experimental data using SPSS 13.0 software into the statistical analysis, the experimental results as mean ± standard deviation (x ± s), related groups of One-way ANOVA test among the groups using LSD or Tamhane test, P lt; 0.05 determined to be statistically significant. : 1.1.0MHz frequency ultrasonic strength of 1.0 ~ 2.0W/cm2 60s Movement intensity-dependent inhibition of MDA-MB-231 cells and PMNC cell growth, and its inhibition: 50% PMNC and MDA-MB-231 cell growth ultrasonic intensity. 1.23 W/cm2 and 1.25 W/cm2, respectively, the corresponding intensity ultrasound similar to the breast cancer cell line MDA-MB-231 and normal human monocytes PMNC killing effect. 0.1mg/ml ~ 1.6mg/ml chlorin e6 concentration-dependent inhibition of MDA-MB-231 cells and PMNC cell growth inhibition of MDA-MB-231 cells and PMNC cell growth IC50 values ??were 0.38mg/ml and 0.77mg/ml, MDA-MB-231 cells more sensitive to the role of Chlorin e6. 2.0.5W/cm2 × 60s × 1.0MHz ultrasound and 0.05mg/ml ~ 0.2mg/ml Chlorin e6 no inhibit PMNC cell growth (ultrasound group Welch test F = 141.792, P = 0.000, ultrasound 0.5W / cm2 group P = 1.000, compared with the control group showed no significant difference; the chlorin e6 group F = 64.468, P = 0.000, by LSD method detection group difference, 0.05mg/ml ~ 0.2mg/ml Compared to the control, P values ??were 0.951,0.952,0.915 were not statistically different), the combination significantly inhibited the growth of MDA-MB-231 cells (F = 66.099, P = 0.000, through LSD method detection group difference, Ultrasound combined with the 0.05mg/ml ~ 0.2mg/ml chlorin e6 groups P = 0.000, significant difference compared with the control group). Cell morphology observed ultrasound combined chlorin-e6 group of MDA-MB-231 cells increase in the number of deaths, compared with ultrasound alone (0.5W/cm2 × 60s × 1.0MHz) and chlorin-e6 (0.2mg/mL) the degree of injury is significantly increased, significantly reduced the proportion of intact cells, cell debris can see more. The second part of chlorin e6-mediated acoustic power combined with adriamycin the breast cancer fine MDA-MB-231's in vitro ultrasound, chlorin Chlorin e6 SDT role with the first part of the experiment, on this basis, the use of adriamycin and SDT combined with adriamycin treatment of MDA-MB-231 cells, and 45 min after MTT (MTT) assay for measuring cell growth. SPSS 13.0 software, the experimental results the mean ± standard deviation (x ± s), the relevant groups of One-way ANOVA test, LSD or Tamhane test P lt; 0.05 judgment was considered statistically significant among the groups . The results showed: 1.1.0MHz frequency the strength for 0.5 to 2.0W/cm2 the ultrasound 60s and the 0.05mg/ml ~ 1.6mg/ml Chlorin e6 growth of MDA-MB-231 cells with the first part of the experiment . SDT role 2.0.5W/cm2 × 60s × 1.0MHz ultrasound and 0.05mg/ml ~ 0.2mg/ml Chlorin e6 combination of the two results, see the first part of the experiment. 3.0.1μg/ml ~ 0.4μg/ml doxorubicin no inhibition of MDA-MB-231 cell growth 4.0.5W/cm2 × 60s × 1.0MHz ultrasound and 0.1mg/ml Chlorin e6 sonodynamic therapy combined with 0.1 μg / ml ~ 0.4μg/ml doxorubicin showed a the adriamycin concentration-dependent inhibition of the growth of MDA-MB-231 cells, and compared to the sound power and doxorubicin group were more pronounced inhibition of the growth of MDA-MB-231 cells (Welch inspection, F = 141.431, P = 0.000 within the via Tamhane law group test drawn: the combined treatment group compared with separate sonodynamic group and separate adriamycin doxorubicin 0.1μg/ml and 0.2μg / ml joint sonodynamic group compared with the separate sonodynamic group, P = 1.000 outside, the rest of the P lt; 0.05, the difference was statistically significant); different timing can produce different inhibitory effects, sound and dynamic action Houjiarue mold hormone group than the first adriamycin, (SDT doxorubicin) sound power group (doxorubicin SDT), more significantly inhibit the growth of breast cancer cells (Welch inspection, F = 141.431, P = 0.000, via Tamhane method on group test: the concentration of doxorubicin were 0.1μg/ml, 0.2μg/ml, 0.4μg/ml, the SDT the corresponding concentrations of doxorubicin group compared with the corresponding concentrations of doxorubicin SDT group, P values ??were 0.000,0.038,0.006, a statistically significant difference). The Conclusion: Chlorin e6 mediated sonodynamic specific inhibition of breast cancer cells MDA-MB-231 growth is expected to become a new sonosensitizer for sonodynamic the treatment of breast cancer. Chlorin e6 acoustic power combined with ADM significantly inhibit breast cancer cells MDA-MB-231 growth, and the role of sound power with doxorubicin than with doxorubicin sonodynamic more pronounced inhibition of the growth of breast cancer cells more significantly inhibited the growth of breast cancer cells, with a timing effect.
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