DT-13 通过调节脂肪细胞微环境中的 PLOD2 抑制乳腺癌转移。
DT-13 suppresses breast cancer metastasis by modulating PLOD2 in the adipocytes microenvironment.
机构信息
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, China.
出版信息
Phytomedicine. 2019 Jun;59:152778. doi: 10.1016/j.phymed.2018.12.001. Epub 2018 Dec 2.
BACKGROUND
Metastasis is the main cause of death in breast cancer and previous researches have indicated the pivotal role of adipocytes in breast cancer metastasis. DT-13, the saponin monomer 13 of the Dwarf lilyturf tuber, has been proved to exert potential anti-metastatic effect, the detailed mechanisms have not been well elucidated and the role of DT-13 in modulating adipocyte-breast cancer microenvironment has been given little attention.
PURPOSE
This study aims to explore the mechanisms of DT-13 in inhibiting breast cancer metastasis and whether DT-13 inhibit breast cancer metastasis via modulating the interactions between adipocytes and breast cancer cells.
METHODS
The cytotoxic effect of DT-13 on breast cancer cell viability was detected by MTT assay. Migration assays was used to conduct the effect of DT-13 on breast cancer cells migration. Orthotopic xenograft tumor model was used to test the effect of DT-13 on breast cancer metastasis. qRT-PCR and Western blot were used to investigate the mechanisms of DT-13 inhibiting breast cancer metastasis.
RESULTS
DT-13 inhibited breast cancer cells migration at the concentration without cytotoxicity. Furthermore, DT-13 decreased PLOD2 expression through modulating JAK/STAT3 and PI3K/AKT signaling pathways directly or indirectly in the adipocyte-breast cancer microenvironment. Orthotopic implantation mouse model of breast cancer further confirmed that DT-13 inhibited breast cancer metastasis via downregulating PLOD2 in vivo.
CONCLUSION
DT-13 suppressed breast cancer metastasis via reducing the expression of PLOD2.
背景
转移是乳腺癌死亡的主要原因，先前的研究表明脂肪细胞在乳腺癌转移中起关键作用。舞鹤芋甾体皂苷单体 13（DT-13）已被证明具有潜在的抗转移作用，但详细机制尚未阐明，其在调节脂肪细胞-乳腺癌微环境中的作用尚未得到重视。
目的
本研究旨在探讨 DT-13 抑制乳腺癌转移的机制，以及 DT-13 是否通过调节脂肪细胞与乳腺癌细胞之间的相互作用来抑制乳腺癌转移。
方法
采用 MTT 法检测 DT-13 对乳腺癌细胞活力的细胞毒性作用。采用迁移实验检测 DT-13 对乳腺癌细胞迁移的影响。采用原位异种移植肿瘤模型检测 DT-13 对乳腺癌转移的影响。采用 qRT-PCR 和 Western blot 检测 DT-13 抑制乳腺癌转移的机制。
结果
DT-13 在无细胞毒性浓度下抑制乳腺癌细胞迁移。此外，DT-13 通过直接或间接调节脂肪细胞-乳腺癌微环境中的 JAK/STAT3 和 PI3K/AKT 信号通路，下调 PLOD2 的表达。乳腺癌原位植入小鼠模型进一步证实，DT-13 通过体内下调 PLOD2 抑制乳腺癌转移。
结论
DT-13 通过降低 PLOD2 的表达抑制乳腺癌转移。
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