【摘要】 肺癌死亡率居世界肿瘤首位,5年生存率不足15%,顺铂耐药是死亡率居高不下的重要原因,本文将探讨光敏剂MPPa介导的光动力疗法诱导人非小细胞肺癌顺铂耐药株A549/DDP发生凋亡的现象及其机制。课题组分别给予不同浓度光敏剂MPPa(0、1、2、4、8、16μmol/L)、不同能量光照(0、0.6、1.2、2.4、3.6、4.8J/cm2)处理细胞,CCK-8法检测细胞活性。将细胞分为对照组、MPPa组(2μmol/L MPPa)、光照组(2.4J/cm2光能量密度)和MPPa介导光动力组(PDT组)(2μmol/L MPPa、2.4J/cm2光能量密度)。应用Anne-V/PI双染流式细胞技术检测细胞凋亡;DCFH-DA染色观察细胞内活性氧产生;蛋白质印迹法(Western blot)检测B淋巴细胞瘤-2(Bcl-2)蛋白和Bcl-2相关X蛋白(Bax)的表达。实验结果显示,单纯光照及MPPa对细胞生长无抑制作用;MPPa介导光动力却对人肺癌耐顺铂细胞A549/DDP有显著杀伤作用,其杀伤作用呈明显的剂量效应关系(P<0.05);PDT组发生凋亡率均高于各对照组(P<0.05);DCFH-DA染色发现PDT组细胞内活性氧明显高于各对照组;Western blot检测发现PDT组Bax蛋白表达升高,Bcl-2蛋白表达降低。实验证实MPPa介导的光动力疗法可抑制肺癌顺铂耐药细胞A549/DDP活性,并诱导其凋亡。更多还原

【Abstract】 Lung cancer is the leading cause of cancer-related deaths worldwide.Despite the development and use of several targeting drugs for lung cancer therapy,the five-year survival rate has remained as low as 15%for the past three decades.Cisplatin-based chemotherapy is considered the first-line therapeutic strategy for lung cancer.However,developments of chemoresistance is a major obstacle for the successful treatment.Therefore,the development of novel therapy against cisplatin-resistance lung cancer is imperative.Photodynamic therapy(PDT),which is a non-invasive combinatorial therapeutic modality using light,photosensitizer(PS)and oxygen,may provide an unprecedented tool to develop more effective treatments.To provide experimental basis for its application in cisplatin-resistance lung cancer,we will discuss the biological effects of MPPa-photodynamic therapy in human cisplatin-resistance lung cancer cells in this article.Human cisplatin-resistance lung cancer cells A549/DDP were co-cultured with MPPa(0,1,2,4,8,16μmol/L)and exposed to light(0,0.6,1.2,2.4,3.6,4.8J/cm2),and cell viability was determined with CCK-8assay.Flow cytometry was used to detect apoptosis,DCFH-DA staining was employed to observe reactive oxygen species(ROS),and Western blot was used to detect the expressions of B-cell lymphoma-2(Bcl-2)protein and Bcl-2associated X protein(Bax).The proliferation of A549/DDP cells was suppressed by PDT.The apoptotic rate in the PDT group was significantly higher than that in the control,MPPa or light group(P<0.05).The level of ROS was increased.The expression of Bax was increased,and that of Bcl-2was decreased.MPPa-photodynamic therapy can significantly suppress cell viability,and induce apoptosis in human cisplatin-resistance lung cancer cells.更多还原