Suzhou TCM Hospital, Affiliated to Nanjing University of Chinese Medicine, , Nanjing, China.
School of Medicine, Shanghai University, Shanghai, China.
Cancer Chemother Pharmacol. 2021 Apr;87(4):487-499. doi: 10.1007/s00280-020-04198-7. Epub 2021 Jan 5.
Bone is the most common late metastasis of breast cancer. Bone metastasis causes not only severe bone pain, but also bone-related diseases such as pathological fractures, which are closely related to osteoclasts. The effects of demethoxycurcumin (DMC) on osteoclast biology has not been investigated. In this study, we explored the effects of DMC on MDA-MB-231 cells, MCF-7 cells, and osteoclasts induced by RANKL in vitro, as well as the protective effect on bone destruction of tumor bone metastasis in vivo. DMC showed inhibitory effect on the migration and promotes the apoptosis of MDA-MB-231 and MCF-7 cells. At the same time, DMC inhibited osteoclast maturation and mature osteoclast bone resorption in a dose-dependent manner, and suppressed the expression of osteoclast marker genes TRAP, CTSK, MMP9, V-ATPase-d2 and DC-STAMP significantly. Biochemical data showed that DMC inhibited tumor cells and osteoclasts by inhibiting the early activation of ERK and JNK MAPK pathway. Consistent with the results in vitro, we confirmed that DMC protects bone destruction caused by tumor metastasis in vivo. In short, our study confirmed that DMC could be used as a potential drug for the treatment of tumor bone destruction.
骨是乳腺癌最常见的晚期转移部位。骨转移不仅会引起严重的骨痛，还会导致与破骨细胞相关的骨相关疾病，如病理性骨折。目前尚未研究去甲氧基姜黄素（DMC）对破骨细胞生物学的影响。在这项研究中，我们探讨了 DMC 对体外 RANKL 诱导的 MDA-MB-231 细胞、MCF-7 细胞和破骨细胞的作用，以及对肿瘤骨转移致骨破坏的体内保护作用。DMC 对 MDA-MB-231 和 MCF-7 细胞的迁移具有抑制作用，并促进其凋亡。同时，DMC 呈剂量依赖性抑制破骨细胞成熟和成熟破骨细胞的骨吸收，并显著抑制破骨细胞标志物基因 TRAP、CTSK、MMP9、V-ATPase-d2 和 DC-STAMP 的表达。生化数据表明，DMC 通过抑制 ERK 和 JNK MAPK 通路的早期激活来抑制肿瘤细胞和破骨细胞的活性。与体外结果一致，我们证实 DMC 可在体内保护肿瘤转移引起的骨破坏。总之，我们的研究证实 DMC 可作为治疗肿瘤性骨破坏的潜在药物。
