超甲氨蝶呤耐药骨肉瘤细胞的去恶性化与组蛋白标记 H3K9me3 和 H3K27me3 的甲基化增加有关。
Loss of Malignancy of Super-Methotrexate-resistant Osteosarcoma Cells Is Associated With an Increase of Methylated Histone Marks H3K9me3 and H3K27me3.
机构信息
AntiCancer Inc., San Diego, CA, U.S.A.;
Department of Surgery, University of California, San Diego, La Jolla, CA, U.S.A.
出版信息
Anticancer Res. 2024 Oct;44(10):4213-4218. doi: 10.21873/anticanres.17251.
BACKGROUND/AIM: Methotrexate (MTX) resistance in osteosarcoma results in a very poor patient prognosis. We previously reported that super MTX-resistant osteosarcoma (143B-MTX) cells, selected from parental 143B osteosarcoma (143B-P) cells by culturing them with increasing concentrations of MTX, exhibited reduced malignancy, despite the over-expression of oncogenes. The present study explored the mechanism of reduced malignancy in the super MTX-resistant osteosarcoma cells.
MATERIALS AND METHODS
Previously selected 143B-MTX cells which are 5,500 times more MTX resistant than parental cells, were used for this study. The status of methylated histone H3K9me3 and H3K27me3 marks was examined with western immunoblotting and compared between 143B-MTX and parental 143B-P cells.
RESULTS
Histone H3K9me3 and H3K27me3 marks were over-expressed in 143B-MTX compared to 143B-P (p<0.05, p<0.01, respectively).
CONCLUSION
Over-expression of histone H3K9me3 and H3K27me3 marks may be related to super-MTX resistance and to the loss of malignancy of super MTX-resistant osteosarcoma cells due to the fundamental relationship of methylation and cancer.
背景/目的：骨肉瘤中甲氨蝶呤（MTX）耐药导致患者预后极差。我们之前报道过，从亲本骨肉瘤（143B-P）细胞中通过培养增加 MTX 浓度筛选出的超级 MTX 耐药骨肉瘤（143B-MTX）细胞尽管过表达癌基因，但恶性程度降低。本研究旨在探讨超级 MTX 耐药骨肉瘤细胞恶性程度降低的机制。
材料和方法
本研究使用先前筛选出的对 MTX 耐药 5500 倍的 143B-MTX 细胞。用 Western 免疫印迹法检测甲基化组蛋白 H3K9me3 和 H3K27me3 标记物的状态，并在 143B-MTX 和亲本 143B-P 细胞之间进行比较。
结果
与 143B-P 相比，143B-MTX 中组蛋白 H3K9me3 和 H3K27me3 标记物过度表达（p<0.05，p<0.01）。
结论
组蛋白 H3K9me3 和 H3K27me3 标记物的过度表达可能与超级 MTX 耐药和超级 MTX 耐药骨肉瘤细胞恶性程度降低有关，因为甲基化与癌症之间存在着根本的关系。
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