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溶瘤单纯疱疹病毒与放疗联合作用于胰腺癌细胞系。

Synergistic action of oncolytic herpes simplex virus and radiotherapy in pancreatic cancer cell lines.

机构信息

Department of Surgery, Peking Union Medical College Hospital, Beijing, China.

出版信息

Br J Surg. 2010 Sep;97(9):1385-94. doi: 10.1002/bjs.7124.

DOI:10.1002/bjs.7124
PMID:20629009
Abstract

BACKGROUND

Despite much research in chemotherapy and radiotherapy, pancreatic adenocarcinoma remains a fatal disease, highly resistant to all treatment modalities. Recent developments in the field of herpes simplex virus (HSV) engineering have allowed the generation of a number of promising virus vectors for treatment of many cancers, including pancreatic tumours. This study examined the use of one such virus, NV1023, in combination with radiation therapy in pancreatic cancer cell lines.

METHODS

HSV therapy in combination with radiotherapy was investigated in pancreatic cancer cell lines Hs766T, Panc-1 and MIA PaCa-2. Multiple therapy effect analysis was performed by computerized simulation. Mechanisms underlying synergy, such as virus replication and apoptosis, were investigated.

RESULTS

The combination of NV1023 and radiation yielded a synergistic oncolytic effect in all tested pancreatic cancer cell lines, with the greatest effect achieved in MIA PaCa-2. This effect was not mediated by an increase in rapid viral replication, but by a substantial increase in apoptosis.

CONCLUSION

The synergistic oncolytic actions of HSV and radiotherapy observed in pancreatic cancer cell lines encourage further testing of this multimodality treatment.

摘要

背景

尽管在化疗和放疗方面进行了大量研究,但胰腺腺癌仍然是一种致命疾病,对所有治疗方法均具有高度耐药性。单纯疱疹病毒 (HSV) 工程领域的最新进展使得能够生成许多有前途的病毒载体来治疗许多癌症,包括胰腺肿瘤。本研究检查了一种此类病毒 NV1023 与放射疗法联合用于胰腺癌细胞系的情况。

方法

在胰腺癌细胞系 Hs766T、Panc-1 和 MIA PaCa-2 中研究了 HSV 联合放射疗法的治疗效果。通过计算机模拟进行了多种治疗效果分析。研究了协同作用的机制,如病毒复制和细胞凋亡。

结果

NV1023 与放射疗法的联合在所有测试的胰腺癌细胞系中产生了协同的溶瘤作用,在 MIA PaCa-2 中效果最大。这种作用不是通过快速病毒复制的增加介导的,而是通过细胞凋亡的大量增加介导的。

结论

在胰腺癌细胞系中观察到的 HSV 和放射疗法的协同溶瘤作用鼓励进一步测试这种多模态治疗方法。

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