【作者】 刘剑仑； 周忠晓； 黄卓正； 欧超；

【Author】 Liu Jianlun,Zhou Zhongxiao,Huang Zhuozheng,Ou Chao Cancer Hospital,Guangxi Medical University,Nanning 530021,China

【机构】 广西医科大学附属肿瘤医院；

【摘要】 目的观察血卟啉衍生物(Hematoporphrphyrin Derivative,HpD)介导的光动力疗法(Photodynamic therapy,PDT)对鼠乳腺癌细胞MA-782动物移植瘤的治疗效果并探讨其作用机制。方法将指数生长期乳腺癌细胞系(MA-782)接种小鼠建立乳腺癌动物模型,随机将荷瘤鼠分为空白对照组,HpD-PDT治疗组(光敏剂浓度为1.0mg/ml,照光强度分别为75J/cm2、150J/cm2、300J/cm2)共4组,肿瘤直径在0.5-1.0cm时进行HpD-PDT;测量各组移植瘤体积变化,光镜、电镜下观察HpD-PDT作用下移植瘤形态学改变,免疫组化检测治疗前及治疗后1 d、3d、7d、14d VEGF、PCNA、Bax和Bcl-2等相关蛋白表达。结果肿瘤直径:与空白对照组比较:HpD-PDT明显抑制肿瘤生长,各组间呈时间、剂量依赖性。肿瘤形态学观察:HpD-PDT后1 d作用于肿瘤血管最为明显,3d肿瘤细胞凋亡最为典型,坏死程度随时间延长更加明显。免疫组织化学:与对照组比较,各实验组VEGF、PCNA和Bcl-2蛋白表达差异有统计学意义(P<0.05);Bax的表达水平PDT后3d内无明显下降,7d后下降明显。肿瘤细胞坏死程度及各蛋白表达水平呈明显的时效相关性和PDT剂量依赖性。结论 HpD-PDT对小鼠乳腺癌模型肿瘤有明显的杀伤作用,PDT通过损伤肿瘤微循环血管、直接杀伤肿瘤细胞、抑制肿瘤细胞增殖及诱导肿瘤细胞凋亡等途径抑制肿瘤生长,并呈时效相关性和PDT剂量依赖性。更多还原

【Abstract】 Objective:To observe the effect of hematoporphrphyrin derivative(HpD) mediated photodynamic therapy(PDT) on tumors from implanted breast cancer cells in mice and investigate its mechanisms.Methods:72 femal mice underwent subcutaneous injection of breast cancer cells of the line MA-782.Ten days later when tumors were formed,the mice were randomly divided into three groups to be treated with HpD-PDT of the concentration of l.Omg/ml, and optical doses of 75 J/cm2,150 J/cm2,300 J/cm2 respectively,and 12 mice were used as normal control group.The tumor size was measured and the change of morphology was observed under light microscope and electron microscope, and VEGF,PCNA,Bax and Bcl-2 were detected by immunohistochemistry at ld,3d,7d and 14d after treatment of HpD-PDT.Results:The growth velocity of tumor of the mice in HpD-PDT groups was all slower than that of the control group.Morphology of the tumor tissues was singnificantly changeable under the light microscopy and electron microscopy.The expression levels of VEGF,PCNA,and Bcl-2 of HpD-PDT groups were significantly lower than those of the control group(P<0.05).There was no difference in the expression of Bax at 1st and 3rd day comparison with the control group after treatment(P>0.05),and at 7th day and 14th day,there were significant difference among all groups(P<0.05).The degree of tumor cell necrosis and expression of VEGF,PCNA,Bcl-2 and Bax protein were related to time- and dose-dependently of PDT.Conclusions:HpD-PDT may inhibit the growth of breast cancer by the way of injuring vessels,promote the process of cellular necrosis and induce apoptosis which was related to time- and dose-dependently of PDT.更多还原