国际医药卫生导报
國際醫藥衛生導報
국제의약위생도보
INTERNATIONAL MEDICINE & HEALTH GUIDANCE NEWS
2014年
12期
1657-1660
,共4页
α干扰素%阿霉素%骨肉瘤%凋亡%天冬氨酸特异性半胱氨酸蛋白酶
α榦擾素%阿黴素%骨肉瘤%凋亡%天鼕氨痠特異性半胱氨痠蛋白酶
α간우소%아매소%골육류%조망%천동안산특이성반광안산단백매
IFN α%Doxorubicin%Osteosarcoma%Apoptosis%Caspases
目的 探讨α干扰素(Interferonα,IFNα)联合化疗药物阿霉素诱导人骨肉瘤U2OS细胞凋亡的作用及其机制,为提高骨肉瘤化疗敏感性探索新的治疗方法.方法 应用台盼蓝拒染法测定IFNα和阿霉素单用以及联用对U2OS细胞的生长抑制作用;Hoechst33258荧光染色检测细胞凋亡形态学变化;Western blot法检测Caspase-3、PARP的活化;采用Caspase抑制剂Z-VAD-FMK预处理各组细胞,检测该作用是否依赖Caspase.结果 IFN α处理24 h、48 h、72 h对U2OS细胞无抑制作用,却明显增强阿霉素诱导的生长抑制作用,具有时间依赖性;联合用药72 h后U2OS细胞出现更为明显的凋亡形态学变化;联合用药组的凋亡关键酶Caspase-3、PARP均发生断裂活化;Caspase抑制剂Z-VAD-FMK预处理明显减弱联合用药引起的生长抑制.结论 IFNα通过Caspase依赖性凋亡通路增强阿霉素诱导的骨肉瘤U2OS细胞生长抑制和凋亡,二者联合应用可能成为提高骨肉瘤化疗敏感性的有效途径.
目的 探討α榦擾素(Interferonα,IFNα)聯閤化療藥物阿黴素誘導人骨肉瘤U2OS細胞凋亡的作用及其機製,為提高骨肉瘤化療敏感性探索新的治療方法.方法 應用檯盼藍拒染法測定IFNα和阿黴素單用以及聯用對U2OS細胞的生長抑製作用;Hoechst33258熒光染色檢測細胞凋亡形態學變化;Western blot法檢測Caspase-3、PARP的活化;採用Caspase抑製劑Z-VAD-FMK預處理各組細胞,檢測該作用是否依賴Caspase.結果 IFN α處理24 h、48 h、72 h對U2OS細胞無抑製作用,卻明顯增彊阿黴素誘導的生長抑製作用,具有時間依賴性;聯閤用藥72 h後U2OS細胞齣現更為明顯的凋亡形態學變化;聯閤用藥組的凋亡關鍵酶Caspase-3、PARP均髮生斷裂活化;Caspase抑製劑Z-VAD-FMK預處理明顯減弱聯閤用藥引起的生長抑製.結論 IFNα通過Caspase依賴性凋亡通路增彊阿黴素誘導的骨肉瘤U2OS細胞生長抑製和凋亡,二者聯閤應用可能成為提高骨肉瘤化療敏感性的有效途徑.
목적 탐토α간우소(Interferonα,IFNα)연합화료약물아매소유도인골육류U2OS세포조망적작용급기궤제,위제고골육류화료민감성탐색신적치료방법.방법 응용태반람거염법측정IFNα화아매소단용이급련용대U2OS세포적생장억제작용;Hoechst33258형광염색검측세포조망형태학변화;Western blot법검측Caspase-3、PARP적활화;채용Caspase억제제Z-VAD-FMK예처리각조세포,검측해작용시부의뢰Caspase.결과 IFN α처리24 h、48 h、72 h대U2OS세포무억제작용,각명현증강아매소유도적생장억제작용,구유시간의뢰성;연합용약72 h후U2OS세포출현경위명현적조망형태학변화;연합용약조적조망관건매Caspase-3、PARP균발생단렬활화;Caspase억제제Z-VAD-FMK예처리명현감약연합용약인기적생장억제.결론 IFNα통과Caspase의뢰성조망통로증강아매소유도적골육류U2OS세포생장억제화조망,이자연합응용가능성위제고골육류화료민감성적유효도경.
Objective To study the effect of IFN α on doxorubicin-induced apoptosis in human osteosarcoma U2OS cells and its molecular mechanisms.Methods Cell growth inhibition was evaluated using Trypan blue exclusion assay.Apoptosis was studied using Hoechst33258 staining.Activation of Caspase-3 and PARP was detected by Western blot.Cells were pre-treated with Caspase van inhibitor Z-VAD-FMK to determine whether the effect caused by IFN α/doxorubicin was caspase-dependent.Results IFN α treatment for 24 h,48 h,and 72 h did not induce growth inhibition but greatly enhanced doxorubicin-induced cytotoxicity in U2OS cells.The combination of IFN α and doxorubicin induced more obvious apoptotic morphological changes.Caspase-3 and PARP were cleaved to yield active fragment following IFN α/doxorubicin combination in U2OS cells,compared with other groups.Z-VAD-FMK pre-treatment obviously decreased the growth inhibition caused by IFN α/doxorubicin combination.Conclusions IFN α enhances doxorubicin-induced growth inhibition and apoptosis in human osteosarcoma U2OS cells through caspase-dependent pathway.It implies that rationally combining IFN α with chemotherapy may be a useful strategy for improving the chemosensitivity of osteosarcoma.
