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ReoT3D、CPT-11 和 BBI608 对小鼠结直肠癌细胞的协同抗癌作用。

The synergistic anticancer effects of ReoT3D, CPT-11, and BBI608 on murine colorectal cancer cells.

机构信息

Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Hematology and cell therapy, Tarbiat Modares University, Tehran, Iran.

出版信息

Daru. 2020 Dec;28(2):555-565. doi: 10.1007/s40199-020-00361-w. Epub 2020 Aug 15.

Abstract

BACKGROUND

Many types of oncolytic viruses (OVs) were enrolled in clinical trials. Recently, an OV named Talimogene laherparepvec approved for the treatment of melanoma. This achievement highlighted the clinical application of OVs. Scientists focus on using these anticancer agents in combination with the current or/and new anticancer chemotherapeutics. They aim to increase the oncolytic effect of a new approach for the treatment of cancer cells.

OBJECTIVES

The present study aimed to assess the anticancer impacts of ReoT3D, irinotecan (CPT-11), and napabucasin (BBI608) against murine colorectal cancer cells (CT26). They are assessed alone and in combination with each other.

METHODS

Here, oncolytic reovirus was propagated and titrated. Then MTT assay was carried out to assess the toxicity of this OV and chemotherapeutics effect on CT26 cells. The anticancer effects of ReoT3D, CPT-11, and BBI608, alone and simultaneously, on CT26 cell line, were assessed by the induction of apoptosis, cell cycle arrest, colony-forming, migration, and real-time PCR experiments.

RESULTS

Alone treatment with ReoT3D, CPT-11, and BBI608 led to effectively inducing of apoptosis, cell cycle arrest, and apoptotic genes expression level and significantly reduce of colony-forming, migration, and anti-apoptotic genes expression rate. Importantly, the maximum anticancer effect against CT26 cell line was seen upon combination ReoT3D, CPT-11, and BBI608 treatment.

CONCLUSION

The present study highlights that combination of ReoT3D, CPT-11, and BBI560 showed synergistic anticancer activity against CT26 cell line. This modality might be considered as a new approach against colorectal cancer (CRC) in the in vivo and clinical trial investigations.

摘要

背景

许多类型的溶瘤病毒(OVs)已被纳入临床试验。最近,一种名为替莫唑胺拉培帕韦的 OV 获批用于治疗黑色素瘤。这一成就凸显了 OVs 的临床应用。科学家们专注于将这些抗癌药物与当前或/和新的抗癌化疗药物联合使用。他们旨在提高新方法治疗癌细胞的溶瘤效果。

目的

本研究旨在评估溶瘤呼肠孤病毒 ReoT3D、伊立替康(CPT-11)和萘巴硼沙(BBI608)单独和联合使用对鼠结直肠癌细胞(CT26)的抗癌作用。

方法

在这里,增殖和滴定溶瘤呼肠孤病毒。然后通过 MTT 法评估该 OV 和化疗药物对 CT26 细胞的毒性作用。通过诱导细胞凋亡、细胞周期阻滞、集落形成、迁移和实时 PCR 实验评估 ReoT3D、CPT-11 和 BBI608 单独和同时对 CT26 细胞系的抗癌作用。

结果

单独使用 ReoT3D、CPT-11 和 BBI608 可有效诱导细胞凋亡、细胞周期阻滞和促凋亡基因表达水平,显著降低集落形成、迁移和抗凋亡基因表达率。重要的是,联合使用 ReoT3D、CPT-11 和 BBI608 对 CT26 细胞系的抗癌效果最大。

结论

本研究强调,ReoT3D、CPT-11 和 BBI608 的联合使用对 CT26 细胞系表现出协同抗癌活性。这种方式可能被认为是体内和临床试验研究中治疗结直肠癌(CRC)的新方法。

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Current understanding of reovirus oncolysis mechanisms.呼肠孤病毒溶瘤机制的当前认识。
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