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黄芩苷通过诱导细胞凋亡对骨靶向性乳腺癌的骨保护和抗肿瘤作用。

Bone-protective and anti-tumor effect of baicalin in osteotropic breast cancer via induction of apoptosis.

机构信息

Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China.

Department of Galactophore, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China.

出版信息

Breast Cancer Res Treat. 2020 Dec;184(3):711-721. doi: 10.1007/s10549-020-05904-y. Epub 2020 Sep 16.

Abstract

PURPOSE

Research suggested that bone is the specific target organ for breast cancer metastasis. The related tumor causes significant morbidity due to a reduction in quality of life and physical function. Increased osteoclast function is implicated in the bone microenvironment during the outgrowth of breast cancer. In the present experimental study, we examined the potential bone-protective effect of baicalin osteotropic breast Cancer and explored the possible mechanism of action.

METHODS

In vitro cell viability effect of baicalin was assessed on the breast cancer cell lines (MDA-MB-231 and MCF-7). We also estimated the in vitro osteoclast and bone resorption. Further, baicalin-regulated osteoblastogenesis and osteoclastogenesis were also estimated in vitro. Finally, the role of the baicalin in the expansion of osteolytic bone disease was scrutinized in a breast cancer bone metastases model.

RESULTS

Baicalin significantly (p < 0.001) downregulated the viability of murine and human cancer cell lines and diminished the osteoclastogenesis of osteoclast progenitors via estimation with the help of qRT-PCR. Baicalin showed the downregulation in the mRNA expression of OCN and ALP. Baicalin reduced the TRAP-positive cells in the presence of RANKL. Baicalin considerably upregulated the cytochrome c secretion into the cytoplasm. Baicalin markedly increased the DNA fragmentation, caspase-3, caspase-8, and caspase-9. Baicalin significantly (p < 0.001) reduced the metastatic growth of MDA-MB-231 cells,preserving the bone mass in a bone metastasis model.

CONCLUSION

Collectively, we can conclude that these results highlight the bone-protective effect of baicalin, which also highlighted the anti-tumor effect; further research is needed into the likely effects on bone health in the bone metastases and osteoporosis populations, such as post-menopausal women with breast cancer.

摘要

目的

研究表明,骨骼是乳腺癌转移的特定靶器官。相关肿瘤会导致生活质量和身体功能显著下降,从而造成严重的发病率。在乳腺癌的生长过程中,破骨细胞功能的增强与骨微环境有关。在本实验研究中,我们研究了黄芩苷对乳腺癌的潜在骨保护作用,并探讨了其可能的作用机制。

方法

采用细胞活力测定法评估黄芩苷对乳腺癌细胞系(MDA-MB-231 和 MCF-7)的体外细胞活力效应。我们还估计了体外破骨细胞和成骨细胞的吸收作用。进一步,我们还在体外评估了黄芩苷对成骨细胞和破骨细胞形成的调节作用。最后,在乳腺癌骨转移模型中研究了黄芩苷在骨溶解骨病扩展中的作用。

结果

黄芩苷显著(p<0.001)下调了鼠类和人类癌细胞系的活力,并通过 qRT-PCR 评估降低了破骨细胞前体的破骨细胞生成。黄芩苷显示出 OCN 和 ALP 的 mRNA 表达下调。黄芩苷减少了 RANKL 存在时的 TRAP 阳性细胞。黄芩苷显著增加了细胞质中细胞色素 c 的分泌。黄芩苷明显增加了 DNA 片段化、caspase-3、caspase-8 和 caspase-9。黄芩苷显著(p<0.001)减少了 MDA-MB-231 细胞的转移性生长,在骨转移模型中保持了骨量。

结论

综上所述,这些结果突出了黄芩苷的骨保护作用,同时也强调了其抗肿瘤作用;需要进一步研究其对骨转移和骨质疏松人群(如乳腺癌绝经后妇女)的骨健康可能产生的影响。

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