维甲酸联合bcl-2反义寡核苷酸诱导肺癌细胞凋亡的研究  

Retinoic acid combined bcl-2 antisense oligodeoxynucleotides induced apoptosis of lung cancer cell line

作　　者：胡俊锋[1] 陈余清[1] 邓静[1] 李殿民[1] 夏雪梅[1] 黄礼年[1] 

机构地区：[1]蚌埠医学院附属医院呼吸内科,安徽蚌埠233004

出　　处：《淮海医药》2005年第1期1-3,共3页Journal of Huaihai Medicine

基　　金：安徽省自然科学基金项目 (2 0 0 1kj178

摘　　要：目的　探讨全反式维甲酸 (all- trans retinoic acid,ATRA)和 bcl- 2反义寡核苷酸 (antisense oligodeoxynucleotides,ASODN)对肺癌的作用及机制 ,寻找肺癌治疗的新途径。方法　采用不同浓度的 ATRA单用或联用 bcl- 2 ASODN和 bcl- 2无义寡核苷酸 (nonsense oligodeoxynucleotides,NSODN)处理 SH- 77细胞 ,通过苔盼蓝拒染实验检测细胞活力 ,MTT法检测细胞生长抑制率 ,流式细胞术检测细胞周期分布、细胞凋亡和 BCL- 2蛋白的表达。结果　不同浓度的 ATRA和 bcl- 2 ASODN对 SH- 77细胞均有抑制生长和诱导凋亡作用 ,G1 / G0 期细胞比例升高 ,S期细胞比例降低 ,增殖指数 (PI)降低 ,凋亡指数 (AI)和 AI/ PI比值升高 ;BCL- 2蛋白比例下降明显。 ATRA(10 - 6 m ol/ L)与 bcl- 2 ASODN两者联用与两者分别单用或与对照组比较差异均有显著性 (P<0 .0 5 )。结论　 ATRA和 bcl- 2 ASODN对 S- 77细胞的生长均有抑制作用 ,同时可诱导其凋亡 ,降低其 BCL - 2蛋白表达 ,两者联用时抗癌作用进一步加强 。Objective To investigate combined effect and mechanism of both ATRA and bcl-2 ASODN in the induction of apoptosis and BCL-2 protein expression of human small cell lung cancer(SCLC) cell line SH-77.Methods SCLC cell line SH-77 was treated with ATRA at different concentration or combined with bcl-2 ASODN and Nonsense oligodeoxynucleotides(NSODN).Multiparameter such as cell growth inhibition rate,proliferation index(PI) and apoptosis index(AI) and BCL-2 protein expression was detected by typan blue stainning,MTT and flow cytometry(FCM).Results Different concentration's ATRA and bcl-2 ASODN inhibited SH-77 cell line cell growth and induced cell apoptosis.G 1/G 0 stage and AI were increased,while cell count at S stage and PI were reduced,decreased BCL-2 protein expression.The effect of ATRA (10 -6mol/L)in combination with ASODN was significant(P<0.05).Conclusion ATRA and bcl-2 ASODN can inhibit SH-77 cell line growth,induce cell apoptosis and reduce BCL-2 protein expression.The combination of ATRA and bcl-2 ASODN could strengthen efficiency of antitumor.bcl-2 ASODN in combination with other modalities for bcl-2 downregulation and may represent an attractive gene regulation-based therapy of lung cancer in the future.

关 键 词：BCL-2 ASODN ATRA 反义寡核苷酸 肺癌 凋亡 细胞 结论 比例 策略 

分 类 号：R735[医药卫生—肿瘤] R734.2[医药卫生—临床医学]