反义小鼠端粒酶RNA及顺铂对小鼠肺癌移植瘤的抑制作用

王安潮; 张永; 陈余清

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反义小鼠端粒酶RNA及顺铂对小鼠肺癌移植瘤的抑制作用

王安潮 , 张永 , 陈余清

文章导航 > 蚌埠医学院学报 > 2005, 30 > 3: (221-223)

引用本文:

Citation:

反义小鼠端粒酶RNA及顺铂对小鼠肺癌移植瘤的抑制作用

蚌埠医学院附属医院呼吸病科, 安徽蚌埠 233004

作者简介: 王安潮(1937-),男,安徽巢湖人,主任医师,教授.

中图分类号: R734.2

The inhibitory effects of antisense mTR and cisplatin on transplantable lung carcinoma in mice

Department of Respiratory Diseases, Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China
CLC number: R734.2

摘要: 目的: 探讨顺铂(DDP)及硫代修饰的反义寡核苷酸(ASODN)对小鼠肺癌移植瘤的抑制作用以及对瘤体、肝脏和睾丸组织中端粒酶活性的影响。方法: 建立肿瘤模型,以荷瘤小鼠的Lewis肺腺癌制成肺癌单细胞悬液(细胞数约1×10⁷/ml)接种健康C57雄性小鼠44只,待移植瘤体积约500mm³时(第9天),按随机方法分成6组;Ⅰ组非治疗组,腹腔注射生理盐水;Ⅱ组腹腔注射反义端粒酶RNA (mTR),1次/日×6天;Ⅲ、Ⅳ和Ⅴ组于第15天腹腔注射不同浓度DDP1次;Ⅵ组联合使用反义mTR及DDP。另设健康对照组,腹腔注射生理盐水,1次/日×6天。PCR-ELISA法测定端粒酶活性。结果: 肿瘤体积缩小及端粒酶活性均以Ⅴ、Ⅵ组显著,与其余各组比较差异均有显著性(P<0.01);Ⅱ组与Ⅰ组及健康对照组肝脏及睾丸端粒酶活性差异均无显著性(P>0.05)。Ⅳ、Ⅴ、Ⅵ组端粒酶活性下降与健康对照组及Ⅰ组差异均有显著性(P<0.01);Ⅴ组较Ⅵ组端粒酶活性下降更显著(P<0.01);Ⅵ组与Ⅱ组端粒酶活性有明显不同(P<0.01),但与Ⅳ组比较差异均无显著性(P>0.05)。结论: ASODN单独使用对肿瘤体积以及肝脏和睾丸端粒酶活性均无明显影响,但对移植瘤端粒酶活性有抑制作用。单用DDP及DDP和反义mTR联合使用均可使移植瘤体积缩小、肿瘤发生坏死、抑制其端粒酶活性,且联合使用均较等剂量单药对肿瘤体积及端粒酶活性抑制作用增强,提示DDP联合针对端粒酶RNA的反义寡核苷酸对肿瘤的抑制有协同作用。
- 肺肿瘤 /
- 肺癌移植瘤 /
- 反义寡核苷酸 /
- 顺铂 /
- 端粒酶 /
- 小鼠
Abstract: Objective: To determine the inhibitory effects of cisplantin and sulfur-modified antisense oligodexyribonucleotide(ASODN) on the growth of transplantable lung carcinoma in mice and on the telomerase activity of carcinoma,liver and testis.Methods: Lewis lung glandular carcinoma cells(1×10P>7P>/ml) were inoculated subcutaneously to 44 C57 male mice.They were randomized into 6 groups.From the 10th day on,0.5 ml 0.9%NS and antisense mTR were intraperitoneally given to group Ⅰ and groupⅡ,respectively,every day for 6 days;0.5 ml DDP of different concentration,1.0 mg/kg,2.0 mg/kg and 4.0 mg/kg,were intraperitoneally injected on the 15th day once in Ⅲ, Ⅳ and Ⅴ groups,respectively;DDP and ASODN combined were applied to group Ⅵ.The telomerase activities of tumor,liver and testis were determined sermi-quantatativly by TRAP-ELASA.Results: Volumes of mice transplantable carcinoma in groups Ⅴ and Ⅵ were greatly reduced(P<0.01) comparing with other groups.The telomerase activity of mice carcinoma in groups Ⅴ and Ⅵ was the lowest(P<0.01) in contrast to other groups.Mice liver and testis telomerase activity in groups Ⅳ,Ⅴand Ⅵ presented significant reduction(P<0.05-P<0.01) in contrast to health control group and groupⅠ.In addition,the liver and testis telomerase activity of group Ⅱ showed no significant reduction(P>0.05) in contrast to groupⅠand healthy contrast group.Conclusions: ASODN alone have no effects on tumor growth and liver and testis telomerase activity,but has inhibitory effect on the telomerase activity of transplantable lung carcinoma.Treatment with DDP alone or in combination with ASODN and DDP demonstrates apparent carcinoma volume shrinkage,carcinoma necrosis and telomerase activity inhibition.Combination of DDP and ASODN has cooperative effect on transplantable lung carcinoma.
- lung neoplasms /
- transplantable lung cancer /
- antisense oligodexyribonucleotide /
- cisplatin /
- telomerase /
- mice

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反义小鼠端粒酶RNA及顺铂对小鼠肺癌移植瘤的抑制作用

作者简介: 王安潮(1937-),男,安徽巢湖人,主任医师,教授.

蚌埠医学院附属医院呼吸病科, 安徽蚌埠 233004

收稿日期: 2005-01-13

关键词:

摘要: 目的: 探讨顺铂(DDP)及硫代修饰的反义寡核苷酸(ASODN)对小鼠肺癌移植瘤的抑制作用以及对瘤体、肝脏和睾丸组织中端粒酶活性的影响。方法: 建立肿瘤模型,以荷瘤小鼠的Lewis肺腺癌制成肺癌单细胞悬液(细胞数约1×10⁷/ml)接种健康C57雄性小鼠44只,待移植瘤体积约500mm³时(第9天),按随机方法分成6组;Ⅰ组非治疗组,腹腔注射生理盐水;Ⅱ组腹腔注射反义端粒酶RNA (mTR),1次/日×6天;Ⅲ、Ⅳ和Ⅴ组于第15天腹腔注射不同浓度DDP1次;Ⅵ组联合使用反义mTR及DDP。另设健康对照组,腹腔注射生理盐水,1次/日×6天。PCR-ELISA法测定端粒酶活性。结果: 肿瘤体积缩小及端粒酶活性均以Ⅴ、Ⅵ组显著,与其余各组比较差异均有显著性(P<0.01);Ⅱ组与Ⅰ组及健康对照组肝脏及睾丸端粒酶活性差异均无显著性(P>0.05)。Ⅳ、Ⅴ、Ⅵ组端粒酶活性下降与健康对照组及Ⅰ组差异均有显著性(P<0.01);Ⅴ组较Ⅵ组端粒酶活性下降更显著(P<0.01);Ⅵ组与Ⅱ组端粒酶活性有明显不同(P<0.01),但与Ⅳ组比较差异均无显著性(P>0.05)。结论: ASODN单独使用对肿瘤体积以及肝脏和睾丸端粒酶活性均无明显影响,但对移植瘤端粒酶活性有抑制作用。单用DDP及DDP和反义mTR联合使用均可使移植瘤体积缩小、肿瘤发生坏死、抑制其端粒酶活性,且联合使用均较等剂量单药对肿瘤体积及端粒酶活性抑制作用增强,提示DDP联合针对端粒酶RNA的反义寡核苷酸对肿瘤的抑制有协同作用。

English Abstract

The inhibitory effects of antisense mTR and cisplatin on transplantable lung carcinoma in mice

Department of Respiratory Diseases, Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China

Received Date: 2005-01-13

Abstract: Objective: To determine the inhibitory effects of cisplantin and sulfur-modified antisense oligodexyribonucleotide(ASODN) on the growth of transplantable lung carcinoma in mice and on the telomerase activity of carcinoma,liver and testis.Methods: Lewis lung glandular carcinoma cells(1×10P>7P>/ml) were inoculated subcutaneously to 44 C57 male mice.They were randomized into 6 groups.From the 10th day on,0.5 ml 0.9%NS and antisense mTR were intraperitoneally given to group Ⅰ and groupⅡ,respectively,every day for 6 days;0.5 ml DDP of different concentration,1.0 mg/kg,2.0 mg/kg and 4.0 mg/kg,were intraperitoneally injected on the 15th day once in Ⅲ, Ⅳ and Ⅴ groups,respectively;DDP and ASODN combined were applied to group Ⅵ.The telomerase activities of tumor,liver and testis were determined sermi-quantatativly by TRAP-ELASA.Results: Volumes of mice transplantable carcinoma in groups Ⅴ and Ⅵ were greatly reduced(P<0.01) comparing with other groups.The telomerase activity of mice carcinoma in groups Ⅴ and Ⅵ was the lowest(P<0.01) in contrast to other groups.Mice liver and testis telomerase activity in groups Ⅳ,Ⅴand Ⅵ presented significant reduction(P<0.05-P<0.01) in contrast to health control group and groupⅠ.In addition,the liver and testis telomerase activity of group Ⅱ showed no significant reduction(P>0.05) in contrast to groupⅠand healthy contrast group.Conclusions: ASODN alone have no effects on tumor growth and liver and testis telomerase activity,but has inhibitory effect on the telomerase activity of transplantable lung carcinoma.Treatment with DDP alone or in combination with ASODN and DDP demonstrates apparent carcinoma volume shrinkage,carcinoma necrosis and telomerase activity inhibition.Combination of DDP and ASODN has cooperative effect on transplantable lung carcinoma.