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细胞食物对放射治疗或放化疗联合治疗的影响:临床前证据。

The effect of CELLFOOD on radiotherapy or combined chemoradiotherapy: preclinical evidence.

作者信息

Nuvoli Barbara, Amadio Bruno, Cortese Giancarlo, Benedetti Serena, Antoniani Barbara, Soriani Antonella, Carosi Mariantonia, Strigari Lidia, Galati Rossella

机构信息

Preclinical Models and New Therapeutic Agent Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

SAFU Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

出版信息

Ther Adv Med Oncol. 2019 Oct 13;11:1758835919878347. doi: 10.1177/1758835919878347. eCollection 2019.

Abstract

BACKGROUND

Based on previous observations that the nutraceutical CELLFOOD™ (CF), the 'physiological modulator' that aimed to make oxygen available 'on demand', inhibits the growth of cancer cells, this study was designed to investigate the role of CF in the regulation of hypoxia-inducible factor 1 alpha (HIF1α) and its correlated proteins, phosphoglycerate kinase 1 and vascular endothelial growth factor. Our idea was that CF, acting on HIF1α, in combination with current anticancer therapies could improve their effectiveness.

METHODS

To evaluate the effect of CF in association with radiotherapy and chemotherapy, different human cancer cell lines and mice with mesothelioma were analysed by tumour growth, clonogenic assay, western blot and immunohistochemical analysis.

RESULTS

CF in combination with radiation with or without cisplatin increases the death rate of cancer cells. , 70% of mice treated with CF before the mesothelioma graft did not show any tumour growth, indicating a possible preventive effect of CF. Moreover, in mouse mesothelioma xenografts, CF improves the effect of radiotherapy also in combination with chemotherapy treatment. Immunohistochemical analysis of tumour explants showed that HIF1α expression was reduced by the combination of CF and radiotherapy treatment and even more by the combination of CF and radiotherapy and chemotherapy treatment. Mechanistically, CF increases the fraction of oxygenated cells, making the radiotherapy more effective with a greater production of reactive oxygen species (ROS) that in turn, reduce the HIF1α expression. This effect is amplified by further increase in ROS from chemotherapy.

CONCLUSIONS

Collectively, results from preclinical trials suggest that CF could be a useful intervention to improve the efficacy of radiotherapy or combined treatment strategies and could be a promising treatment modality to counteract cancer.

摘要

背景

基于之前的观察,即营养保健品CELLFOOD™(CF),一种旨在“按需”提供氧气的“生理调节剂”,可抑制癌细胞生长,本研究旨在探讨CF在调节缺氧诱导因子1α(HIF1α)及其相关蛋白磷酸甘油酸激酶1和血管内皮生长因子中的作用。我们的想法是,CF作用于HIF1α,与目前的抗癌疗法联合使用可提高其疗效。

方法

为了评估CF与放疗和化疗联合使用的效果,通过肿瘤生长、克隆形成试验、蛋白质印迹法和免疫组织化学分析,对不同的人类癌细胞系和患有间皮瘤的小鼠进行了分析。

结果

CF与放疗联合使用,无论是否使用顺铂,均可提高癌细胞的死亡率。在间皮瘤移植前用CF治疗的小鼠中,70%未出现任何肿瘤生长,表明CF可能具有预防作用。此外,在小鼠间皮瘤异种移植模型中,CF与化疗联合使用时也可提高放疗效果。对肿瘤外植体的免疫组织化学分析表明,CF与放疗联合治疗可降低HIF1α表达,而CF与放疗及化疗联合治疗时降低幅度更大。从机制上讲,CF可增加氧合细胞比例,使放疗更有效,产生更多的活性氧(ROS),进而降低HIF1α表达。化疗进一步增加ROS可放大这种效应。

结论

总体而言,临床前试验结果表明,CF可能是一种有用的干预措施,可提高放疗或联合治疗策略的疗效,可能是一种有前景的抗癌治疗方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7180/6792276/b81deeb042ea/10.1177_1758835919878347-fig1.jpg

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