摘要
目的观察CpGODN对荷瘤鼠肺癌皮下种植瘤生长和血管生成的作用。方法建立荷瘤鼠皮下种植瘤模型,随机分为4个治疗组:单纯给药组[CpGODN1826(1μg/μl)]、照射给药组[CpGODN1826(1μg/μl)+β射线(RT:8Gy)]、对照照射组[生理盐水(NS:100μl/只)+β射线(RT:8Gy)]、对照组[生理盐水(NS:100μl/只)]。接种肺癌细胞后7d开始瘤内注射药物并照射5d,计算抑瘤率。免疫组化法检测肿瘤组织血管内皮生长因子-C(VEGF-C)、neuropilin-1(NRP-1)的表达,RT-PCR法测定瘤组织中VEGF-CmRNA、NRP-1mRNA的表达。结果在抑瘤率方面,CpGODN1826+RT组抑瘤率为(69.80±26.54)%,显著高于CpGODN1826组(21.5±14.96)%、NS+RT组(15.10±49.45)%和NS组,差异有统计学意义(P<0.01)。四组荷瘤鼠肿瘤组织中VEGF-C的阳性表达率分别为10%(1/10)、50%(5/10)、80%(8/10)、100%(10/10);NRP-1的阳性表达率分别为10%(1/10)、40%(4/10)、90%(9/10)、100%(10/10)。在NRP-1和VEGF-C阳性表达率方面,CpGODN1826+RT组和CpGODN1826组的阳性表达率显著低于NS+RT组和NS组(P<0.01),CpGODN1826+RT组明显低于CpGODN1826组(P<0.01)。VEGF-CmRNA相对表达水平分别为18.34±3.19、29.62±3.14、51.13±2.81、53.46±5.67;NRP-1mRNA相对表达水平分别为23.57±5.73、34.72±5.13、59.95±4.76、62.49±6.34,CpGODN1826+RT组和CpGODN1826组较NS+RT组和NS组显著下降(P<0.01),CpGODN1826+RT组明显低于CpGODN1826组(P<0.01)。结论 CpGODN1826可显著抑制荷瘤鼠种植瘤的生长,其作用机制可能与抑制VEGF-C和NRP-1的表达、抑制血管生成有关。
Objective To investigate the inhibitory effect of CpG ODN on the tumor growth and angiogenesis on lung carcinoma in the nude mice. Methods To estabhsb the nude mice tumor implant models using A549 cells, forty model mice were randomly divided into 4 groups ： CpG ODN1826 （1 μg/μl） group, CpG ODN1826 （1 μg/μl） ＋ RT（ 8 Gy）group, NS ＋ RT group and NS group. Seven days after implantation of cancer cells, different drugs were injected intratumorally for 5. d,and the tumor inhibition rate was calculated. Immunohistochemistry（IHC） image analysis was performed to determine the vascular endothelial growth factor-C （VEGF-C） and Neuropilin-1 （NRP-1）, the expression of VEGF-C mRNA and NRP-1 mRNA in the tumor was identified by RT-PCR. Results The tumor growth inhibitory rate in CpG ODN1826 in combination with RT group（69. 80 ±26. 54） % was significantly higher than that in CpG ODN1826 group, NS ＋ RT group and NS group （P 〈 0. 01 ）. The incidence of positive in the CpG ODN1826 ＋ RT group,CpG ODN1826 group,NS ＋ RT group and NS group,VEGF-C were 10% （1/10） ,50% （5/10） ,80% （8/10）,100% （10/10） ; NRP-1 was 10% （1/10）,40% （4/10）,90% （9/10）,100% （10/10）. The positive rates of NRP-1 and VEGF-C ,with those of the CpG ODN1826 ＋ RT group and CpG ODN1826 group significantly lower than that of the NS ＋ RT group and NS group （ P 〈 0.01 ）, CpG ODN1826 ＋ RT group obviously lower than that of the CpG ODN1826 group（ P 〈0. 01 ）. The relative levels of VEGF-C mRNA in the CpG ODN1826 ＋ RT group, CpG ODN1826 group, NS ＋ RT group and NS group were 18. 34 ± 3.19,29. 62 ±3.14, 51.13±2.81,53.46 ±5.67;NRP-1 mRNA were 23. 57 ±5.73,34.72 ±5.13,59.95 ±4.76,62.49 ±6.34, respectively, with the levels in the CpG ODN1826 ＋ RT groups significantly lower than that in the CpG ODN1826 group（P 〈0. 01 ） ,and CpG ODN1826 ＋ RT groups were obviously lower than that of the CpG ODN1826 group（P 〈 0. 01 ）. Conclusions CpG ODN1826 can remarkably inhibit the growth of nude mice tumor, and its mechanism might be relative to inhibiting the expression of VEGF-C, NRP-1 and angiogenesis.
出处
《中华临床医师杂志（电子版）》
CAS
2012年第12期96-100,共5页
Chinese Journal of Clinicians(Electronic Edition)
