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溶瘤病毒塞内卡病毒A通过诱导细胞周期停滞和凋亡抑制肝细胞癌的增殖与生长。

Oncolytic Virus Senecavirus A Inhibits Hepatocellular Carcinoma Proliferation and Growth by Inducing Cell Cycle Arrest and Apoptosis.

作者信息

Gong Tao, Liu Xiao, Li Qingyuan, Branch Donald R, Loriamini Melika, Wen Wenxian, Shi Yaoqiang, Tan Qi, Fan Bin, Zhou Zhonghui, Li Yujia, Yang Chunhui, Li Shilin, Duan Xiaoqiong, Chen Limin

机构信息

Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, China.

Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan, China.

出版信息

J Clin Transl Hepatol. 2024 Aug 28;12(8):713-725. doi: 10.14218/JCTH.2024.00125. Epub 2024 Jun 20.

Abstract

BACKGROUND AND AIMS

Hepatocellular carcinoma (HCC) is a highly aggressive tumor with limited treatment options and high mortality. Senecavirus A (SVA) has shown potential in selectively targeting tumors while sparing healthy tissues. This study aimed to investigate the effects of SVA on HCC cells and and to elucidate its mechanisms of action.

METHODS

The cell counting kit-8 assay and colony formation assay were conducted to examine cell proliferation. Flow cytometry and nuclear staining were employed to analyze cell cycle distribution and apoptosis occurrence. A subcutaneous tumor xenograft HCC mouse model was created using HepG2 cells, and Ki67 expression in the tumor tissues was assessed. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and hematoxylin and eosin staining were employed to evaluate HCC apoptosis and the toxicity of SVA on mouse organs.

RESULTS

, SVA effectively suppressed the growth of tumor cells by inducing apoptosis and cell cycle arrest. However, it did not have a notable effect on normal hepatocytes (MIHA cells). In an setting, SVA effectively suppressed the growth of HCC in a mouse model. SVA treatment resulted in a significant decrease in Ki67 expression and an increase in apoptosis of tumor cells. No notable histopathological alterations were observed in the organs of mice during SVA administration.

CONCLUSIONS

SVA inhibits the growth of HCC cells by inducing cell cycle arrest and apoptosis. It does not cause any noticeable toxicity to vital organs.

摘要

背景与目的

肝细胞癌(HCC)是一种侵袭性很强的肿瘤,治疗选择有限且死亡率高。A 组柯萨奇病毒(SVA)已显示出在选择性靶向肿瘤同时 sparing 健康组织方面的潜力。本研究旨在探讨 SVA 对 HCC 细胞的影响并阐明其作用机制。

方法

采用细胞计数试剂盒-8 法和集落形成试验检测细胞增殖。运用流式细胞术和核染色分析细胞周期分布及凋亡发生情况。使用 HepG2 细胞建立皮下肿瘤异种移植 HCC 小鼠模型,并评估肿瘤组织中 Ki67 的表达。采用末端脱氧核苷酸转移酶 dUTP 缺口末端标记法和苏木精-伊红染色评估 HCC 凋亡及 SVA 对小鼠器官的毒性。

结果

SVA 通过诱导凋亡和细胞周期停滞有效抑制肿瘤细胞生长。然而,它对正常肝细胞(MIHA 细胞)没有显著影响。在体内环境中,SVA 有效抑制小鼠模型中 HCC 的生长。SVA 治疗导致 Ki67 表达显著降低且肿瘤细胞凋亡增加。在给予 SVA 期间,小鼠器官未观察到明显的组织病理学改变。

结论

SVA 通过诱导细胞周期停滞和凋亡抑制 HCC 细胞生长。它对重要器官不会造成任何明显毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45e5/11310753/874f7f5320d8/JCTH-12-713-g001.jpg

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