研究动态
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水稻破烂矮化病毒基因组对小鼠模型乳腺癌生长和转移的免疫刺激作用。

The immunostimulant effects of the rice ragged stunt virus genome on the growth and metastasis of breast cancer in mouse model.

发表日期:2023 Nov 01
作者: Nejad Mohammadi, Fatemeh Nouri, Yazdan Asgari, Hemen Moradi-Sardareh, Mahnaz Sharafi-Kolkeshvandi, Hossein Nemati, Gholam Ali Kardar
来源: INTERNATIONAL IMMUNOPHARMACOLOGY

摘要:

据报道,乳腺癌有多种治疗策略,但仍然需要新的有效疗法。刺激免疫系统及其成分对抗癌细胞是免疫疗法的独特治疗策略之一,而长dsRNA在这方面具有免疫刺激作用。基于生物信息学方法,根据其免疫原性,选择并合成了水稻破烂特技RNA病毒基因组片段。基于体外转录技术,合成了dsRNA,并通过凝胶阻滞实验验证了其与PEI/PEI-Ac聚乙烯亚胺(PEI)或乙酰化聚乙烯亚胺(PEI-Ac)的结合能力。然后,通过在PEI上添加乙酰基合成了PEI-Ac,1H NMR方法结果表明其合成成功。 Balb/C 小鼠中 4 T1 细胞诱导癌症后,通过 PEI/PEI-Ac-dsRNA 进行腹膜内 (IP) 和瘤内 (IT) 治疗,并评估肿瘤生长抑制作用。结果表明,PEI/PEI-Ac-dsRNA 可导致 IP 和 IT 途径中肿瘤重量和体积的减少。此外,通过使用宏观转移结节计数以及苏木精和伊红 (H
There are multiple treatment strategies that have been reported for breast cancer, while new and effective therapies against it are still necessary. Stimulating the immune system and its components against cancer cells is one of the unique treatment strategies of immunotherapy and long dsRNAs are immunostimulant in this regard. Based on bioinformatics approaches, a fragment of the Rice ragged stunt RNA virus genome was selected and synthesized according to its immunogenicity. Based on the in vitro transcription technique, dsRNA was synthesized and its binding ability to the PEI/PEI-Ac Polyethylenimine (PEI) or Acetylated polyethylenimine (PEI-Ac) was verified by the gel retardation assay. Then, the PEI-Ac was synthesized by adding acetyl groups to the PEI, and the results of the 1H NMR method indicated its successful synthesis. After cancer induction by 4 T1 cells in Balb/C mice, intraperitoneal (IP) and intratumoral (IT) treatment by the PEI/PEI-Ac-dsRNA were performed and the tumor growth inhibition was evaluated. Results demonstrated that PEI/PEI-Ac-dsRNA can lead to a decrease in tumor weight and volume in both the IP and IT routes. Also, by using macro-metastatic nodule counting and hematoxylin and eosin (H&E) staining we showed that PEI/PEI-Ac-dsRNA can prevent micro and macro-metastasis in the lung. Therefore, the PEI/PEI-Ac-dsRNA acts as an effective inhibitor of growth and metastasis of the breast cancer models. We showed that viral dsRNA can exert its antitumor properties by stimulating TNF-α and IFN-γ. In general, our results revealed that dsRNA derived from the plant virus genome stimulates the intrinsic immune system and can be a potential immune stimulant drug for cancer treatment.Copyright © 2023 Elsevier B.V. All rights reserved.