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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白对MDA-MB-231和MCF-7乳腺癌细胞生长、表型及其对辐射诱导凋亡敏感性的影响

EFFECTS OF SARS-COV-2 SPIKE PROTEIN ON THE GROWTH AND PHENOTYPE OF MDA-MB-231 AND MCF-7 BREAST CANCER CELLS AND THEIR SENSITIVITY TO RADIATION-INDUCED APOPTOSIS.

作者信息

Brichenko V, Shlapatska L, Zavelevich M, Zvarych L, Panchenko V, Lyaskivska O, Skachkova O, Golyarnik N, Abramenko I, Buchynska L, Chumak A

机构信息

Національний науковий центр радіаційної медицини, гематології та онкології Національної Академії медичних наук України, Київ, Україна.

Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького Національної Академії наук України, Київ, Україна.

出版信息

Exp Oncol. 2025 Jul 11;47(1):24-33. doi: 10.15407/exp-oncology.2025.01.024.

DOI:10.15407/exp-oncology.2025.01.024
PMID:40674167
Abstract

BACKGROUND

The coronavirus infection caused by SARS-Cov-2 virus, in addition to the development of severe acute respiratory syndrome, is responsible for the development of a multiple organ dysfunction syndrome. An important aspect is its relationship with cancer. The data from clinical and experimental studies are contradictory. Thus, further studies are needed to elaborate on the potential effects of SARS-Cov-2 on cancer cells.

AIM

To study the effect of SARS-Cov-2 spike protein (SP) on the survival, phenotype, and sensitivity to radiation-induced apoptosis of breast cancer (BC) cell lines of different molecular subtype (MDA-MB-231 and MCF-7).

MATERIALS AND METHODS

The effects of SARS-Cov-2 SP on MDA-MB-231 and MCF-7 cells were assessed using the cell proliferation assay and flow cytometry (Ki-67, CD44, CD133, CD105, CD90, CD10, CD5, CD19, and p53). The sensitivity to radiationinduced apoptosis was evaluated by 7-amino-actinomycin D and propidium iodide staining.

RESULTS

We did not find any significant short-term effect of SP on the proliferative activity of both studied cell lines. The phenotype of MDA-MB-231 cells cultured with SP changed toward a decrease in CD105+CD90+ and CD105+CD90- subpopulations (p < 0.0001). The p53 expression increased both in SP-treated MDA-MB-231 and MCF-7 cells. The sensitivity of SP-treated MDA-MB-231 and MCF-7 cells to radiation-induced apoptosis, although insignificantly, increased. Apoptosis in irradiated MDA-MB-231 cells was accompanied by a two-fold increase in the fluorescence intensity of p53 in SP-treated MDA-MB-231 cells. In both irradiated cultures, a significant increase in the percent of cells in S-phase after SP treatment was observed compared to SP-untreated cells.

CONCLUSION

Since most vaccines are based on SP expression, the obtained data might have a certain significance in the study of the effect of anti-SARS-Cov-2 vaccination on tumor growth and the sensitivity of cancer cells to cytoreduction therapies.

摘要

背景

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的冠状病毒感染,除了会引发严重急性呼吸综合征外,还会导致多器官功能障碍综合征。一个重要方面是它与癌症的关系。临床和实验研究的数据相互矛盾。因此,需要进一步研究以阐明SARS-CoV-2对癌细胞的潜在影响。

目的

研究SARS-CoV-2刺突蛋白(SP)对不同分子亚型乳腺癌(BC)细胞系(MDA-MB-231和MCF-7)的存活、表型以及辐射诱导凋亡敏感性的影响。

材料与方法

使用细胞增殖测定法和流式细胞术(检测Ki-67、CD44、CD133、CD105、CD90、CD10、CD5、CD19和p53)评估SARS-CoV-2 SP对MDA-MB-231和MCF-7细胞的影响。通过7-氨基放线菌素D和碘化丙啶染色评估辐射诱导凋亡的敏感性。

结果

我们未发现SP对两种研究细胞系的增殖活性有任何显著的短期影响。用SP培养的MDA-MB-231细胞的表型朝着CD105+CD90+和CD105+CD90-亚群减少的方向变化(p<0.0001)。在经SP处理的MDA-MB-231和MCF-7细胞中,p53表达均增加。经SP处理的MDA-MB-231和MCF-7细胞对辐射诱导凋亡的敏感性虽不显著,但有所增加。在经SP处理的MDA-MB-231细胞中,辐射诱导凋亡的MDA-MB-231细胞中p53的荧光强度增加了两倍。与未用SP处理的细胞相比,在两种辐射培养物中,经SP处理后S期细胞百分比均显著增加。

结论

由于大多数疫苗基于SP表达,所得数据可能在研究抗SARS-CoV-2疫苗接种对肿瘤生长以及癌细胞对细胞减灭疗法敏感性的影响方面具有一定意义。

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