PO.IM03.01 · 免疫学
斯庞德威尼病毒对子宫内膜癌来源的 HEC-1-A 细胞具有高度溶瘤活性
Spondweni virus is highly oncolytic in endometrial carcinoma-derived HEC-1-A cells
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
子宫内膜腺癌约占所有子宫内膜癌的 80%,每年影响超过 400,000 名女性。疾病进展至晚期时,5 年生存率从 81% 降至 15%。此前,本实验室发现寨卡病毒(ZKV)具有令人鼓舞的溶瘤和抗肿瘤活性,可在卵巢癌和子宫内膜癌的小鼠异种移植模型中缩小肿瘤体积。斯庞德威尼病毒(SPN)是一种黄病毒,在系统发育上与 ZKV 相关,但在免疫学上与之不同。与 ZKV 感染一样,大多数人类 SPN 感染为无症状。我们假设 SPN 会表现出与 ZKV 类似的溶瘤活性。子宫内膜腺癌细胞系 HEC-1-A 来源于一例 IA 期子宫内膜肿瘤,被选用于接受三种 ZKV 毒株(MR766、ZIKV-A1 和 ZIKV A-2)和一种 SPN 毒株(SPN A-1)的感染。我们采用病毒空斑试验、AlamarBlue™ 细胞活力测定和蛋白质印迹,检测 ZKV 和 SPN 感染的 HEC-1-A 细胞中的病毒复制,测量 NS-1 和病毒包膜蛋白表达,并比较病毒感染后的细胞死亡率。我们的数据表明,HEC-1-A 细胞对 SPN 比对 ZKV 更易感。这一发现为 SPN 作为溶瘤疗法提供了见解,并为探索其在其他癌症类型中的应用开辟了道路。
查看英文原文 English abstract
Endometrial adenocarcinoma accounts for approximately 80% of all endometrial cancers, affecting more than 400,000 women per year. With advanced disease, the 5-year survival rate drops from 81% to 15%. Previously, our laboratory found that Zika virus (ZKV) has promising oncolytic and anti-tumor activities, reducing tumor volume in murine xenograft models of ovarian and endometrial cancer. Spondweni (SPN) is a flavivirus phylogenetically related to but immunologically distinct from ZKV. Like ZKV infection, most human SPN infections are asymptomatic. We hypothesized that SPN would exhibit oncolytic activity like that of ZKV. The endometrial adenocarcinoma cell line HEC-1-A, which was derived from a stage IA endometrial tumor, was selected for infection with three ZKV strains (MR766, ZIKV-A1, and ZIKV A-2) and one SPN strain (SPN A-1). Using viral plaque assays, AlamarBlue™ cell viability assays, and western blots, we examined viral replication in ZKV- and SPN-infected HEC-1-A cells, measuring NS-1 and viral envelope protein expression, and comparing rates of cell death following viral infection. Our data indicated that HEC-1-A cells are more susceptible to SPN than to ZKV. This discovery provides insight into SPN as an oncolytic therapy and opens the door to exploring its use in other cancer types.
利益披露 Disclosure
C. Collins, None..
E. Gearhart, None..
C. Finn, None..
R. Venkataraman, None..
P. Phelan, None..
K. Alexander, None.