Full Text:   <1375>

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CLC number: R735.7

On-line Access: 2019-11-21

Received: 2019-02-23

Revision Accepted: 2019-08-30

Crosschecked: 2019-10-08

Cited: 0

Clicked: 2658

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Yan-Jing Gao

https://orcid.org/0000-0001-8153-3754

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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.12 P.1003-1013

http://doi.org/10.1631/jzus.B1900089


A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth


Author(s):  Yu-Huan Bai, Xiao-Jing Yun, Yan Xue, Ting Zhou, Xin Sun, Yan-Jing Gao

Affiliation(s):  Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, China; more

Corresponding email(s):   gaoyanjing@sdu.edu.cn

Key Words:  Hepatocellular carcinoma, Oncolytic adenovirus, Golgi protein 73, Sphingosine kinase 1


Yu-Huan Bai, Xiao-Jing Yun, Yan Xue, Ting Zhou, Xin Sun, Yan-Jing Gao. A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth[J]. Journal of Zhejiang University Science B, 2019, 20(12): 1003-1013.

@article{title="A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth",
author="Yu-Huan Bai, Xiao-Jing Yun, Yan Xue, Ting Zhou, Xin Sun, Yan-Jing Gao",
journal="Journal of Zhejiang University Science B",
volume="20",
number="12",
pages="1003-1013",
year="2019",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900089"
}

%0 Journal Article
%T A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth
%A Yu-Huan Bai
%A Xiao-Jing Yun
%A Yan Xue
%A Ting Zhou
%A Xin Sun
%A Yan-Jing Gao
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 12
%P 1003-1013
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%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900089

TY - JOUR
T1 - A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth
A1 - Yu-Huan Bai
A1 - Xiao-Jing Yun
A1 - Yan Xue
A1 - Ting Zhou
A1 - Xin Sun
A1 - Yan-Jing Gao
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 12
SP - 1003
EP - 1013
%@ 1673-1581
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1900089


Abstract: 
Objective: To evaluate the inhibitory role of a novel oncolytic adenovirus (OA), GP73-SphK1sR-Ad5, on the growth of hepatocellular carcinoma (HCC). Methods: GP73-SphK1sR-Ad5 was constructed by integrating golgi protein 73 (GP73) promoter and sphingosine kinase 1 (SphK1)-short hairpin RNA (shRNA) into adenovirus serotype 5 (Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells. The expression of SphK1 and adenovirus early region 1 (E1A) was detected by quantitative real-time PCR (qRT-PCR) and western blot, respectively. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and apoptotic rate was determined by flow cytometry. An Huh7 xenograft model was established in mice injected intratumorally with GP73-SphK1sR-Ad5. Twenty days after injection, the tumor volume and weight, and the survival time of the mice were recorded. The histopathological changes in tumor tissues were observed by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Results: Transfection of GP73-SphK1sR-Ad5 significantly upregulated E1A and downregulated SphK1 in Huh7 cells, but not in HL7702 cells. GP73-SphK1sR-Ad5 transfection significantly decreased the viability and increased the apoptotic rate of Huh7 cells, but had no effect on HL7702 cells. Intratumoral injection of GP73-SphK1sR-Ad5 into the Huh7 xenograft mouse model significantly decreased tumor volume and weight, and prolonged survival time. It also significantly decreased the tumor infiltration area and blood vessel density, and increased the percentages of cells with nucleus deformation and cells with condensed chromatin in tumor tissues. Conclusions: GP73-SphK1sR-Ad5 serves as a novel OA and can inhibit HCC progression with high specificity and efficacy.

一种新的溶瘤腺病毒抑制肝癌细胞的生长

目的:研究新型溶瘤腺病毒GP73-SphK1sR-Ad5对肝癌细胞生长的抑制作用.
创新点:GP73-SphK1sR-Ad5是一种新型的溶瘤腺病毒,可以特异及有效地抑制肝癌细胞生长,为肝癌的临床治疗提供新思路.
方法:通过整合高尔基体蛋白73(GP73)及鞘氨基醇激酶1(SphK1)构建了GP73-SphK1sR-Ad5腺病毒,进而转染肝癌Huh7细胞及正常HL7702肝细胞.通过实时定量PCR和蛋白印记实验检测SphK1E1A基因的表达;通过四氮唑盐比色分析法(MTT法)检测细胞活力;通过流式细胞术检测细胞凋亡率.构建Huh7异种移植小鼠模型,并注射GP73-SphK1sR-Ad5腺病毒.20天后,记录小鼠肿瘤体积和重量,以及存活时间.用苏木精-伊红(HE)染色法和透射电镜(TEM)观察肿瘤组织的病理变化.
结果:GP73-SphK1sR-Ad5转染显著上调了Huh7细胞中E1A的表达,下调了SphK1的表达,降低了细胞活性,并提高了凋亡率,然而对HL7702细胞无明显影响.Huh7异种移植小鼠模型内注射GP73-SphK1sR-Ad5显著降低了肿瘤的体积和重量,延长了小鼠的存活时间,并降低了肿瘤组织中的肿瘤浸润面积、血管密度及核变形和染色质浓缩的细胞数.
结论:新型溶瘤腺病毒GP73-SphK1sR-Ad5可以特异和有效地抑制肝癌进展.

关键词:肝癌;溶瘤腺病毒;高尔基体蛋白73(GP73);鞘氨基醇激酶1(SphK1)

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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