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双氢青蒿素通过抑制 Akt-CREB-MMP13 信号通路抑制乳腺癌细胞的增殖、迁移和侵袭。

Sauchinone inhibits the proliferation, migration and invasion of breast cancer cells by suppressing Akt-CREB-MMP13 signaling pathway.

机构信息

Department of ICT Environmental Health System, Graduate School, Soonchunhyang University, Asan-si 31538, Republic of Korea.

Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-si 31538, Republic of Korea.

出版信息

Biosci Rep. 2021 Oct 29;41(10). doi: 10.1042/BSR20211067.

Abstract

Sauchinone, a lignan isolated from Saururus chinenesis, is known to exhibit anti-inflammatory and anti-oxidant effects. Recently, sauchinone has been reported to inhibit the growth of various cancer cells, but its effects on breast cancer cells remain poorly understood. In the present study, we investigated the effects of sauchinone on the growth of breast cancer cells along with the underlying molecular mechanisms. Our results show that sauchinone treatment markedly inhibited the proliferation, migration, and invasion of breast cancer cells. Sauchinone reduced the phosphorylation of Akt, ERK, and CREB increased by transforming growth factor-β (TGF-β). In particular, sauchinone treatment suppressed the expression of matrix metalloproteinase (MMP)-13 (MMP13) by regulating the Akt-CREB signaling pathway. Sauchinone was less effective in inhibiting cell migration in Mmp13-knockdown cells than in control cells, suggesting that MMP13 may be a novel target for sauchinone. Our study suggests that sauchinone inhibits the growth of breast cancer cells by attenuating the Akt-CREB-MMP13 pathway. In addition, the targeted inhibition of MMP13 by sauchinone represents a promising approach for the treatment of breast cancer.

摘要

从白前中分离得到的木脂素萨楚酮已被证实具有抗炎和抗氧化作用。最近,有报道称萨楚酮能抑制多种癌细胞的生长,但它对乳腺癌细胞的作用仍知之甚少。在本研究中,我们研究了萨楚酮对乳腺癌细胞生长的影响及其潜在的分子机制。结果表明,萨楚酮处理明显抑制了乳腺癌细胞的增殖、迁移和侵袭。萨楚酮降低了转化生长因子-β(TGF-β)诱导的 Akt、ERK 和 CREB 的磷酸化。特别是,萨楚酮通过调节 Akt-CREB 信号通路抑制基质金属蛋白酶(MMP)-13(MMP13)的表达。在 MMP13 敲低细胞中,萨楚酮抑制细胞迁移的效果不如在对照细胞中明显,这表明 MMP13 可能是萨楚酮的一个新靶点。本研究表明,萨楚酮通过减弱 Akt-CREB-MMP13 通路抑制乳腺癌细胞的生长。此外,萨楚酮对 MMP13 的靶向抑制可能为乳腺癌的治疗提供一种有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3445/8561391/1a800631dd45/bsr-41-bsr20211067-g1.jpg

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