Bcl-2反义寡核苷酸对裸鼠人肺癌移植瘤抑制作用的研究(英文)

目的探讨 Bcl-2反义寡核核苷酸(ASODN)对裸鼠人肺癌移植瘤的成瘤能力和生长的抑制作用。方法将经硫代修饰的 Bcl-2 ASODN 导入非小细胞肺癌 NCI-H460细胞内,然后将这种细胞接种于裸鼠皮下,观察肿瘤出现的时间和肿瘤体积的变化,并计算抑瘤率。同时采用未经处理的 NCI-H460细胞接种于裸鼠背部皮下建立裸鼠人肺癌移植瘤模型,待长出瘤结节直径为≥5mm 后,分为 Bcl-2 ASODN 实验组、生理盐水对照组和无义寡核苷酸对照组3组。实验组用15mg/kg ASODN 两天一次直接瘤内注射,连用3周,测肿瘤大小变化和组织形态学改变。结果 Bcl-2 ASODN 作用后的 NCI-H460细胞在裸鼠皮下成瘤能力降低,最大抑瘤率达87.5%(P<0.01)。Bcl-2 ASODN 处理的NCI-H460细胞在裸鼠皮下成瘤的平均时间延长为12.6天(P<0.01)。在治疗 NCI-H460细胞裸鼠移植瘤过程中,生理盐水对照组和无义对照组的瘤块体积进行性增大,而 Bcl-2 ASODN 组的瘤块生长很缓慢,治疗组和两个对照组瘤重相比均有显著性差异(P<0.05)。治疗后第30天剥离瘤块,两个治疗组分别与两个对照组瘤重相比均有显著性差异(P<0.01)。Bcl-2 ASODN 治疗组裸鼠肺癌细胞移植瘤的生长受到明显抑制,抑瘤率为71.0%。瘤块病理学检查可见,Bcl-2 ASODN 治疗组瘤块内有大片的变性坏死灶,结缔组织增生,炎性细胞浸润;而两个对照组瘤体内癌细胞呈弥漫性密集分布。结论 Bcl-2反寡义核苷酸能降低肺癌细胞的成瘤能力,抑制移植瘤生长。

Effect of Bcl-2 Antisense Oligodeoxynucleotides on Human Lung Carcinoma Transplanted Subcutaneously in Nude Mice

Objective:To investigate the inhibitory effects of the Bcl-2 antisense oligodeoxynucleotides (ASODN)on tumor formation and growth of human lung carcinoma transplanted subcutaneously in nude mice.Methods:Human NCI-H460 cells treated with Bcl-2 ASODN or nonesense oligodeoxynucleotide (NSODN)and untreated NCI-H460 cells were respectively implanted subcutaneously into nude mice.When the diameters of tumor were above 0.5 cm after untreated NCI-H460 cells injection,the mice bearing tumor were randomly divided into three groups:saline control group,Bcl-2 ASODN group,NSODN group.ODN was directly injected into the tumor body for 3 weeks.The weight and volume of subcutaneous tumors were measured,and the morphology of tumor cells was observed.Results:The tumorigenic ability of the treated NCI-H460 cells by Bcl-2 ASODN was reduced.The mean time at which tumor can be detected was prolonged up to 12.6 days(P<0.01).The maximum tumor growth inhibitory rate was 87.5%.In therapeutic efficacy,growth of tumor was significantly inhibited in Bcl-2 ASODN group as compared with that in NSODN group,saline-treated group(P<0.01).The NSODN control was ineffective.In comparison with NSODN-treated,saline-treated mice,those treated with Bcl-2 ASODN showed a significant decrease in median weight of subcutaneous tumors(P<0.01).The growth inhibitory rate was 71.0% in ASODN group.Conclusion:Bcl-2 ASODN could inhibit tumor formation and tumor growth in nude mice.