| Breast cancer is one of the malignant tumors in the middle-aged women, and its incidence and mortality are rising year by year. At present, the traditional methods for breast cancer including surgery, radiotherapy, chemotherapy, hormone therapy, etc. they are their own inadequacies exist. And can not prevent and cure cancer effectively. Therefore, exploring new promising approaches for breast cancer therapy is urgently awaits to be solved in the fields of life sciences and medical research. Sonodynamic therapy (SDT) is a novel anticancer approach, which is based on the Photodynamic therapy, mainly using ultrasound can act on the enrichment sound sensitivity agent, focuse at the tumor site, kill the tumor cells specifically and achieve the purpose of treatment of cancer.The distinct advantage of Sonodynamic therapy is targeting and little cytotoxic side effects, high security, as a result its anti-tumor effect has important theoretical significance and clinical application.The research group has found that ProtoporphyrinⅨ,which is an effective sound sensitivity, as an effective ingredient of the hematoporphyrin derivatives, it can achieve the purpose of killing tumor cells by combination with ultrasound through inducing cell apoptosis, cell cycle arrest and autophagy and so on. However, the heterogeneity seen and sensitivity of ultrasound intensity, effectiveness of sonosensitizer are different, they bring about complexity and causations for anti-cancer system of SDT, add difficulties to researches. The anti-tumor mechanism of SDT still stay at stage of verifying different hypothesis, therefore, thorough discussion and expounded the mechanism in the cell molecular biology of anti-tumor effect of SDT,which can drive SDT to be applied to the clinical treatment.On the basis of previous research achievements of our laboratory, the paper was soupported by the ministry of education of specialized research fund for the doctoral program of higher education. In vitro culture of human breast cancer MDA-MB-231 cells were treated with different concentration of PpⅨin the presence of ultrasound, a preliminary study of the PpⅨmediated SDT on MDA-MB-231 cell cycle arrest function and mechanism were undertaken. MTT assay was used to detect the cell livability of different ultrasonic intensity, the cytotoxic effects of MDA-MB-231 cells treated with ultrasound combining with different concentrations of PpⅨwas also detected. The distribution of cell cycle was measured by flow cytometry, the cell cycle protein was measured by western blotting, a preliminary study of the PpⅨmediated SDT on cell cycle arrest were undertaken, so as to provide theoretical basis for clinical of SDT. Present experimental results obtained are as follows:1 When the ultrasonic frequency was 1.1 MHz, the killing effect of different intensity of ultrasounds were intensity dependence:the greater the ultrasound intensity were, the cell viability was decereased. Compared with the control, the survival rate was decereased significantly when the ultrasonic power was 3 W/cm2, it was chosen for the best ultrasonic power.2 The inhibition of ultrasound combined different PpⅨconcertration on breast cancer cells MDA-MB-231 showed a dose-dependpent manner, cell viability decreased significantly after treated with ultrasound combined PpⅨand PpⅨalone when drug concentrations higher than 1μM. PpⅨ-SDT showed a synergistic effect compared with PpⅨalone.3 Flow cytometry was performed to measure the cell cycle at different concentrations of PpⅨand PpⅨ-SDT. The results showed that the distribution of S phase cells increased in both of simple drug group and ultrasound combined with drug group when MDA-MB-231 cells treated with PpⅨand PpⅨ-SDT at different concentrations after 12 h. With the increase of drug concentration, when the concentration of PpⅨwas 10μM, the distribution of S phase cells in simple drug group increased from 42.81% to 52.83%, distribution of S phase cells in PpⅨ-SDT group increased from47.86% to 61.53%. When treated at 24 h, the distribution of S phase cells also increased. With the increase of drug concentration, when the concentration of PpⅨwas 10μM, distribution of S phase cells in simple drug group increased from 44.35% to 52.89%, distribution of S phase cells in PpⅨ-SDT group increased from45.12% to 59.52%. When treated at 48 h, compared with the control group, cell cycle distribution did not change significantly. The results suggest that:certain concentration of PpⅨinhibit the growth breast cancer MDA-MB-231 cells, induce the cell cycle in S phase.4 Cell cycle expression of key proteins of MDA-MB-231 were detected by Western blotting. The results showed that the expression p21 was upregulated, while other proteins such as p53, puma, CDK2 had not significant change afer treated with different concentrations of PpⅨ. While in PpⅨ-SDT group, the expression of p21, p53, and puma were upregulated, CDK2 had little change. |
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