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在伴有肥胖的小鼠宫颈癌模型中，通过全身给予小干扰RNA（siRNA）-中性二油酰磷脂酰胆碱（DOPC）纳米脂质体对人乳头瘤病毒16型E7进行治疗性沉默。

Therapeutic silencing of HPV 16 E7 by systemic administration of siRNA-neutral DOPC nanoliposome in a murine cervical cancer model with obesity.

作者信息

Chapoy-Villanueva Hector, Martinez-Carlin Ivonne, Lopez-Berestein G, Chavez-Reyes Arturo

机构信息

Centro de Investigación y de Estudios Avanzados del IPN, Unidad Monterrey, Nuevo León, Mexico.

出版信息

J BUON. 2015 Nov-Dec;20(6):1471-9.

PMID:26854443

Abstract

PURPOSE

To evaluate the effectiveness of a neutral DOPC nanoliposome system for the delivery of siRNA to tumor cells in an obese murine cervical cancer model.

METHODS

In vitro silencing of E6-E7 mRNA and E7 protein using siRNAE6 or siRNAE7 was analyzed in TC-1 cells by RT-PCR and Western blot. Silencing and antitumor capacities of siRNAE7-DOPC-nanoparticles (NP) were tested in vivo in both normal and obese mice using qPCR. These NPs were administered twice a week for 15 days and tumor volume and weight were recorded.

RESULTS

Levels of in vitro E6-E7 silencing were 90% for mRNA and 60% for protein when siRNAE7 was used. On the other hand when siRNAE6 was used, the levels of silencing were 50% for E6-E7 mRNA and only 20% for protein. In vivo E7 mRNA silencing by siRNAE7-DOPC-NP was similar (60%) in both non-obese and obese mouse models. The therapeutic study showed a 65% decrease in tumor volume and a 57% reduction in tumor weight as compared to the control groups.

CONCLUSION

There was no negative impact of obesity on the antitumor activity of siRNA-DOPC-NP in obese mice.

摘要

目的

评估中性二油酰磷脂酰胆碱（DOPC）纳米脂质体系统在肥胖小鼠宫颈癌模型中向肿瘤细胞递送小干扰RNA（siRNA）的有效性。

方法

通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法，在TC-1细胞中分析使用siRNAE6或siRNAE7对E6-E7信使核糖核酸（mRNA）和E7蛋白进行的体外沉默。使用实时定量聚合酶链反应（qPCR）在正常和肥胖小鼠体内测试siRNAE7-DOPC纳米颗粒（NP）的沉默和抗肿瘤能力。每周两次给予这些纳米颗粒，持续15天，并记录肿瘤体积和重量。

结果

使用siRNAE7时，体外E6-E7沉默水平对于mRNA为90%，对于蛋白质为60%。另一方面，使用siRNAE6时，E6-E7 mRNA的沉默水平为50%，而蛋白质的沉默水平仅为20%。在非肥胖和肥胖小鼠模型中，siRNAE7-DOPC-NP在体内对E7 mRNA的沉默效果相似（60%）。治疗研究显示，与对照组相比，肿瘤体积减少了65%，肿瘤重量减少了57%。