Karagülle Onur Olgaç, Yurttaş Asiye Gök
Department of General Surgery, Istanbul Education and Research Hospital, University of Health Sciences, Cerrahpaşa, Org. Abdurrahman Nafiz Gürman Cd. No:24 Fatih, 34098, İstanbul, Turkey.
Istanbul Health and Technology University, Faculty of Pharmacy, Biochemistry Department, İstanbul, Turkey.
Tissue Cell. 2023 Dec;85:102233. doi: 10.1016/j.tice.2023.102233. Epub 2023 Oct 6.
Luminal-B type human breast cancer cell line (BT-474) to assess the synergistic effects of ozone applied after chemotherapeutic treatment with various dosages of doxorubicin, and compare the results with the effects on L929 fibroblast cell line.
Doxorubicin (1-50 M) was added to each cell lines and left to sit for 24 h at 37 °C. Then, as combination groups, half of the groups were incubated with 30 g/mL ozone for 25 min. Tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), and matrix metalloproteinase-2 and - 9 (MMP-2 and MMP-9) levels were measured using the MTT test, flow cytometry, and immunocytochemistry, respectively.
When compared to simply doxorubicin-applied cells without ozone treatment, each dose of doxorubicin + ozone treatment considerably boosted L929 viability but significantly decreased BT-474 viability. Additionally, the combination increased the apoptotic impact of doxorubicin on BT-474 but not L929 (P < 0.001). TGF-, MMP-2, and MMP-9 levels of L929 after combination were substantially higher than those of the other groups (P < 0.01). Doxorubicin's effect on BT-474's protein levels, which had significantly decreased in comparison to those of the other groups, was reversed by the combination treatment (P < 0.05).
Doxorubicin's anti-proliferative and apoptotic effects were enhanced by ozone treatment in BT-474 cells, but it also repaired and healed healthy fibroblast cells that had been harmed by the cytotoxicity of the chemotherapy drug. If doxorubicin and ozone treatment are coupled, BT-474 cells may develop resistance to it through expressions of TNF-α, TGF-β, MMP-2, and MMP-9.
使用腔面B型人乳腺癌细胞系（BT - 474）评估在不同剂量阿霉素化疗后应用臭氧的协同作用，并将结果与对L929成纤维细胞系的作用进行比较。
将阿霉素（1 - 50 μM）添加到每个细胞系中，并在37℃下放置24小时。然后，作为联合组，一半的组用30 μg/mL臭氧孵育25分钟。分别使用MTT试验、流式细胞术和免疫细胞化学测量肿瘤坏死因子α（TNF-α）、转化生长因子β（TGF-β）以及基质金属蛋白酶-2和-9（MMP-2和MMP-9）水平。
与未进行臭氧处理仅应用阿霉素的细胞相比，各剂量的阿霉素 + 臭氧处理显著提高了L929的活力，但显著降低了BT - 474的活力。此外，联合处理增加了阿霉素对BT - 474的凋亡影响，但对L929没有影响（P < 0.001）。联合处理后L929的TGF-β、MMP-2和MMP-9水平显著高于其他组（P < 0.01）。联合处理逆转了阿霉素对BT - 474蛋白质水平的影响，与其他组相比，其蛋白质水平显著降低（P < 0.05）。
臭氧处理增强了阿霉素在BT - 474细胞中的抗增殖和凋亡作用，但也修复了因化疗药物细胞毒性而受损的健康成纤维细胞。如果将阿霉素和臭氧处理联合使用，BT - 474细胞可能会通过TNF-α、TGF-β、MMP-2和MMP-9的表达产生耐药性。
