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电加热调制增强纳米姜黄素和白藜芦醇对结直肠癌细胞的免疫和抗肿瘤作用。

Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia.

机构信息

Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, 1 Sec 4 Roosevelt Road, Taipei, 10617, Taiwan.

Graduate Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

BMC Cancer. 2020 Jun 29;20(1):603. doi: 10.1186/s12885-020-07072-0.

Abstract

BACKGROUND

Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment.

METHODS

This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment.

RESULTS

The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages.

CONCLUSIONS

The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.

摘要

背景

调制电磁热疗(mEHT)是一种用于癌症治疗的热疗形式。mEHT 已被证明通过诱导热休克蛋白的释放、触发细胞凋亡和破坏细胞膜的完整性来增强肿瘤细胞对化疗药物的细胞摄取,从而激活宿主免疫。姜黄素和白藜芦醇都是植物化学物质,具有有效的抗氧化剂、免疫激活剂和肿瘤发展的潜在抑制剂的功能。然而,生物利用度差是其在临床癌症治疗中应用的主要障碍。

方法

本研究旨在探讨 mEHT 是否可以提高纳米姜黄素和白藜芦醇在体外和体内模型中的抗癌疗效。体外研究包括细胞增殖测定、细胞周期和凋亡分析。分析 SD 大鼠模型中姜黄素和白藜芦醇的血清浓度吸收情况。采用 CT26/BALB/c 动物肿瘤模型验证联合 mEHT/姜黄素/白藜芦醇治疗的安全性、肿瘤生长曲线和肿瘤组织内免疫细胞浸润。

结果

结果表明,mEHT 联合纳米姜黄素和白藜芦醇处理显著诱导 CT26 细胞的细胞周期停滞和凋亡。应用 mEHT 后,姜黄素和白藜芦醇的血清浓度明显升高。该联合治疗还通过诱导肿瘤细胞凋亡和 HSP70 表达,抑制 CT26 结肠癌的生长,同时招募 CD3+T 细胞和 F4/80+巨噬细胞。

结论

本研究结果表明,这种天然、无毒的化合物可能是临床癌症治疗的一种有效抗肿瘤策略。mEHT 可以使潜在抗肿瘤材料的细胞摄取,并为免疫级联反应创造有利的肿瘤微环境,从而提高姜黄素和白藜芦醇联合治疗的成功率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ce3/7324975/e088c984a2c3/12885_2020_7072_Fig1_HTML.jpg

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