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白藜芦醇类似物 HS-1793 通过诱导抗肿瘤免疫增强了放射治疗在乳腺肿瘤生长中的作用。

The resveratrol analogue, HS‑1793, enhances the effects of radiation therapy through the induction of anti‑tumor immunity in mammary tumor growth.

机构信息

Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju‑si, Jeollanam‑do 58245, Republic of Korea.

Department of Research Center, Dong Nam Institute of Radiological and Medical Sciences, Jangan‑eup, Gijang‑gun, Busan 619‑953, Republic of Korea.

出版信息

Int J Oncol. 2020 Jun;56(6):1405-1416. doi: 10.3892/ijo.2020.5017. Epub 2020 Mar 19.

Abstract

Radiotherapy can induce the infiltration of immune suppressive cells which are involved in promoting tumor progression and recurrence. A number of natural products with immunomodulating abilities have been gaining attention as complementary cancer treatments. This attention is partly due to therapeutic strategies which have proven to be ineffective as a result of tumor‑induced immunosuppressive cells found in the tumor microenvironment. The present study investigated whether HS‑1793, a resveratrol analogue, can enhance the antitumor effects by inhibiting lymphocyte damage and immune suppression by regulatory T cells (Tregs) and tumor‑associated macrophages (TAMs), during radiation therapy. FM3A cells were used to determine the role of HS‑1793 in the radiation‑induced tumor immunity of murine breast cancer. HS‑1793 treatment with radiation significantly increased lymphocyte proliferation with concanavalin A (Con A) stimulation and reduced the DNA damage of lymphocytes in irradiated tumor‑bearing mice. The administration of HS‑1793 also decreased the number of Tregs, and reduced interleukin (IL)‑10 and transforming growth factor (TGF)‑β secretion in irradiated tumor‑bearing mice. In addition, HS‑1793 treatment inhibited CD206+ TAM infiltration in tumor tissue when compared to the controls or irradiation alone. Mechanistically, HS‑1793 suppressed tumor growth via the activation of effector T cells in irradiated mice. On the whole, the findings of the present study reveal that HS‑1793 treatment improves the outcome of radiation therapy by enhancing antitumor immunity. Indeed, HS‑1793 appears to be a good therapeutic candidate for use in combination with radiotherapy in breast cancer.

摘要

放疗可诱导免疫抑制细胞浸润,这些细胞参与促进肿瘤进展和复发。许多具有免疫调节能力的天然产物作为癌症的辅助治疗方法引起了人们的关注。之所以引起关注,部分原因是由于肿瘤微环境中存在的肿瘤诱导免疫抑制细胞,导致某些治疗策略无效。本研究旨在探讨白藜芦醇类似物 HS-1793 是否能够通过抑制调节性 T 细胞 (Tregs) 和肿瘤相关巨噬细胞 (TAMs) 对淋巴细胞的损伤和免疫抑制作用,增强放疗的抗肿瘤作用。采用 FM3A 细胞系来确定 HS-1793 在辐射诱导的小鼠乳腺癌肿瘤免疫中的作用。结果发现,与单独放疗相比,HS-1793 联合放疗可显著增加伴 ConA 刺激的淋巴细胞增殖,并减少照射荷瘤小鼠的淋巴细胞 DNA 损伤。HS-1793 给药还可减少 Tregs 的数量,并降低照射荷瘤小鼠的白细胞介素 (IL)-10 和转化生长因子 (TGF)-β 分泌。此外,与对照组或单独放疗相比,HS-1793 治疗可抑制肿瘤组织中 CD206+TAM 的浸润。从机制上讲,HS-1793 通过激活照射小鼠中的效应 T 细胞来抑制肿瘤生长。总之,本研究的结果表明,HS-1793 治疗可通过增强抗肿瘤免疫来改善放疗的效果。实际上,HS-1793 似乎是一种很好的治疗候选药物,可与乳腺癌的放疗联合使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93a4/7170036/fba0e943695d/IJO-56-06-1405-g00.jpg

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