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放疗对乳腺癌患者激活细胞焦亡死亡途径的影响:血清 GSDMD-CT、NLRP3 和 IL-18 的作用。

Effect of Radiotherapy on Activating the Pyroptotic Cell Death Pathway in Breast Cancer Patients: The Role of Serum GSDMD-CT, NLRP3 and IL-18.

机构信息

Radiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

Cancer Management and Research Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.

出版信息

Asian Pac J Cancer Prev. 2024 Feb 1;25(2):447-452. doi: 10.31557/APJCP.2024.25.2.447.

DOI:10.31557/APJCP.2024.25.2.447
PMID:38415529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11077100/
Abstract

BACKGROUND

Breast cancer (BC) is the most common form of cancer among women and the second leading cause of cancer-related death worldwide. Several malignancies can be successfully treated with radiation (RT), although radioresistance is still a major contributor to radiotherapy failure. Ionizing radiation (IR) induces pyroptosis in cancer cells. Pyroptosis is a designed method of death connected to routine immunity and directly related to the body ROS content. Objective for the study: The aim of this work was to investigate the role of serum GSDMD-CT, nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) and IL-18 as predictors of pyroptotic cell death mechanism induced by radiotherapy in breast cancer patients.

SUBJECTS AND METHODS

The 70 female participants in this study were divided into two groups: Group (I): 40 breast cancer patients treated with radiotherapy. Group (II): a control group of 30 healthy volunteers with similar ages and sex. Patients with breast cancer received radiation, with a dose of 44 Gray administered over the course of 16 days in five daily fractions of 2.75 Gray each. Two blood samples were taken from breast cancer patients: one before radiotherapy and the other after radiotherapy. While one blood sample was taken from healthy controls. The levels of the circulating pyroptosis biomarkers IL-18, NLRP3, and GSDMD-CT were measured using the ELISA method.

RESULTS

Our results showed that, there was a significant increase in serum pyroptosis markers GSDMD-CT, NLRP3 and IL-18 in BC Patients after RT when compared to before radiotherapy.

CONCLUSION

Radiotherapy induced pyroptosis in breast cancer patients as a new cell death mechanism. GSDMD-CT, NLRP3 and IL-18 are biomarkers of pyroptosis that significantly increased post irradiation highlighting enhanced ROS and pyroptosis induction.

摘要

背景

乳腺癌(BC)是女性中最常见的癌症类型,也是全球癌症相关死亡的第二大主要原因。尽管放射抵抗仍然是放射治疗失败的主要原因,但几种恶性肿瘤可以通过放射治疗(RT)成功治疗。电离辐射(IR)会在癌细胞中诱导细胞焦亡。细胞焦亡是一种与固有免疫有关的程序性细胞死亡方式,与体内 ROS 含量直接相关。研究目的:本研究旨在探讨血清 GSDMD-CT、核苷酸结合寡聚结构域和富含亮氨酸重复序列家族 pyrin 3(NLRP3)和 IL-18 作为预测乳腺癌患者放射治疗诱导细胞焦亡机制的标志物的作用。

受试者和方法

本研究共纳入 70 名女性参与者,分为两组:组(I):40 名接受放射治疗的乳腺癌患者。组(II):30 名年龄和性别相匹配的健康志愿者对照组。乳腺癌患者接受放射治疗,剂量为 44 Gray,在 16 天内每天 5 次,每次 2.75 Gray。从乳腺癌患者中采集两份血样:一份在放射治疗前,另一份在放射治疗后。从健康对照组中采集一份血样。使用 ELISA 法测量循环细胞焦亡生物标志物 IL-18、NLRP3 和 GSDMD-CT 的水平。

结果

我们的结果表明,与放射治疗前相比,放射治疗后 BC 患者血清细胞焦亡标志物 GSDMD-CT、NLRP3 和 IL-18 显著增加。

结论

放射治疗诱导乳腺癌患者发生细胞焦亡,这是一种新的细胞死亡机制。GSDMD-CT、NLRP3 和 IL-18 是细胞焦亡的生物标志物,放射治疗后显著增加,提示 ROS 和细胞焦亡诱导增强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e12b/11077100/44986e66757d/APJCP-25-447-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e12b/11077100/7c23ef386f91/APJCP-25-447-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e12b/11077100/480ed6736380/APJCP-25-447-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e12b/11077100/44986e66757d/APJCP-25-447-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e12b/11077100/7c23ef386f91/APJCP-25-447-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e12b/11077100/480ed6736380/APJCP-25-447-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e12b/11077100/44986e66757d/APJCP-25-447-g003.jpg

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