光动力疗法联合NS-398对人胆管癌QBC939细胞的抑制作用  

Inhibitory effect of photodynamic therapy combined with NS-398 on human cholangiocarcinoma cell line QBC939

作　　者：姜海涛 范晓翔 高咪咪 陈云杰 Jiang Haitao;Fan Xiaoxiang;Gao Mimi;Chen Yunjie(Department of General Surgery,Hwa Mei Hospital,University of Chinese Academy of Sciences,Ningbo Institute of Life and Health Industry,University of Chinese Academy of Sciences,Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province,Ningbo 315010,China;Department of Interventional Therapy,Hwa Mei Hospital,University of Chinese A cademy of Sciences,Ningbo 315010,China;Department of Gastroenterology,Hwa Mei Hospital,University of Chinese A cademy of Sciences,Ningbo 315010,China)

机构地区：[1]中国科学院大学宁波华美医院外二科,中国科学院大学宁波生命与健康产业研究院,浙江省消化系统肿瘤诊治及研究重点实验室,315010 [2]中国科学院大学宁波华美医院介入治疗科,315010 [3]中国科学院大学宁波华美医院消化内科,315010

出　　处：《中华肝胆外科杂志》2020年第12期938-942,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：华美研究基金(2017HMKY11);浙江省消化系统肿瘤诊治及研究重点实验室(2019E10020);宁波市消化系统肿瘤临床医学研究中心(2019A21003);浙江省医药卫生科研项目(2018265085)。

摘　　要：目的研究光动力疗法(photodynamic therapy,PDT)和选择性环氧合酶-2(cyclooxygenase-2,COX-2)抑制剂NS-398联合对人胆管癌细胞QBC939的抑制作用。方法体外培养人胆管癌QBC939细胞株,分别设立PDT处理组、NS-398浓度组、二者联合组和空白对照组,将血卟啉衍生物(HPD)浓度(0、2、4、6、8、10μg/ml),光照强度(0、5、10、15 J/cm2)和NS-398浓度(0、25、50、100、200μmol/L)分别联合作用;利用CCK8法检测各组处理对QBC939细胞生长的相对抑制率;采用流式细胞实验检测QBC939细胞的凋亡情况;采用Transwell法检测QBC939细胞的体外侵袭情况。结果PDT和NS-398在体外均能单独抑制QBC939细胞生长,HPD浓度8μg/ml,光照强度5 J/cm2联合50μmol/L的NS-398作用后,细胞生长抑制率达95%,二者联合组与PDT处理组、NS-398浓度组和空白对照组比较均有统计学差异(P<0.05),继续增加二者的强度,细胞生长抑制率变化不明显;流式细胞实验表明PDT和NS-398联合作用能够明显促进QBC939细胞的早期凋亡,二者联合组的细胞凋亡率为(66.18±1.22)%,空白对照组、PDT处理组和NS-398浓度组的细胞凋亡率分别为(4.16±1.25)%、(22.19±1.17)%、(23.21±1.65)%,二者联合组与其它三组相比差异均有统计学意义(P<0.05);HPD浓度4μg/ml,光照强度5 J/cm2联合25μmol/L的NS-398作用后,QBC939细胞生长无明显抑制,但其体外侵袭能力降低,二者联合组的侵袭细胞数(8.16±1.65)少于空白对照组(31.22±1.25)、PDT处理组(18.09±1.17)和NS-398浓度组(19.21±1.72),差异具有统计学意义(P<0.05)。结论PDT和NS-398联合作用可以促进QBC939细胞早期凋亡,抑制其侵袭能力,进而起到对QBC939细胞生长的抑制作用。Objective To study the effect and the mechanism of photodynamic therapy(PDT)combined with NS-398 on cholangiocarcinoma QBC939 cell lines.Methods In vitro,QBC939 cells were divided into PDT treatment group,NS-398 concentration group,combined group and blank control group,which were exposed to 0,2,4,6,8,10μg/ml Hematoporphyrin derivative(HPD)with 0,5,10,15 J/cm2 light radiation and 0,25,50,100,200μmol/L NS-398 respectively.The growth of QBC939 cells was determined by CCK8 assay and the growth inhibition ratio was calculated.Flow cytometry and transwell migration assays were used to detect apoptosis and invasion of QBC939 cells respectively.Results PDT combined with NS-398 could significantly suppress the growth of QBC939 cells in vitro(P<0.05).When the concentration of HPD was 8μg/ml,the light radiation was 5 J/cm2 and NS-398 was 50μmol/L,the relative growth inhibition rate of QBC939 cells was about 95%.If the intensity of PDT and NS-398 were increased,no statistical differences were detected.It’s indicated that PDT combined with NS-398 could promote QBC939 cells apoptosis at the early stage through the flow cytometry detection.The rate of apoptosis of QBC939 cells was(66.18±1.22)%in combined group,the apoptotic rate of blank control group,PDT treatment group and NS-398 concentration group were(4.16±1.25)%,(22.19±1.17)%,(23.21±1.65)%respectively,which differences were statistically significant(P<0.05).When the concentration of HPD was 4μg/ml,the light radiation was 5 J/cm2 and NS-398 was 25μmol/L,it had no obviously inhibitory effect on QBC939 cells growth,but could obviously inhibit cells invasion through transwell migration assays.The number of invasive cells in combined group(8.16±1.65)was significantly lower than that in blank control group(31.22±1.25),PDT treatment group(18.09±1.17)and NS-398 concentration group(19.21±1.72),and significant differences were observed between the combined group and the other three groups(P<0.05).Conclusion PDT combined with NS-398 could promote apoptosis and inhib

关 键 词：胆管肿瘤 光动力疗法 环氧合酶2 抑制 

分 类 号：R735.8[医药卫生—肿瘤]