OSW-1通过三阴性乳腺癌抑制NFATc2的肿瘤生长和转移。,Cancer Medicine

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OSW-1通过三阴性乳腺癌抑制NFATc2的肿瘤生长和转移。
Cancer Medicine ( IF 2.9 ) Pub Date : 2020-06-08 , DOI: 10.1002/cam4.3196
Xiaorong Ding _{1,

2} , Yumei Li ₁ , Jun Li ₁ , Yongmei Yin ₁

Affiliation

OSW-1是从虎眼万年青球茎中提取的天然化合物在1992年。已经显示出在各种癌细胞中的强抗肿瘤活性。但是，对OSW-1对乳腺癌肿瘤生长和转移的影响仍然知之甚少。在我们的研究中，我们表明OSW-1对乳腺癌细胞具有很强的抗癌作用，但对正常细胞的毒性较低。因此，它也显示在异种移植模型中OSW-1显着抑制了肿瘤的生长。此外，我们进行了膜联蛋白V / PI标记的流式细胞仪检测和TUNEL检测，并显示OSW-1通过诱导凋亡来抑制肿瘤生长。此外，我们进行了跨孔测定，发现OSW-1通过介导上皮-间质转化显着抑制了三阴性乳腺癌（TNBC）细胞的迁移和侵袭能力。除了，OSW-1还可以抑制原位模型中的转移，与对照组相比，具有更长的生存期。最后，我们进行了RNA测序和细胞功能研究，以研究OSW-1如何抑制TNBC的分子机制，并确定NFATc2可能是OSW-1介导的对细胞死亡，肿瘤生长，侵袭和迁移的影响的关键因素。

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OSW-1 inhibits tumor growth and metastasis by NFATc2 on triple-negative breast cancer.

OSW‐1 is a natural compound extracted from the bulbs of Ornithogalum saundersiae in 1992. It has been shown strong antitumor activities in various cancer cells. However, the effects of OSW‐1 on tumor growth and metastasis in breast cancer are still poorly understood. In our research, we showed that OSW‐1 had a strong anticancer effect on breast cancer cells, but lower toxicity to normal cells. Accordingly, it also revealed significant inhibition of tumor growth by OSW‐1 in xenograft model. In addition, we performed Annexin V/PI‐labeled flow cytometric assay and TUNEL assay and showed that OSW‐1 inhibited tumor growth by inducing apoptosis. Furthermore, we carried out transwell assays and found that OSW‐1 significantly repressed the migratory and invasive capabilities of triple‐negative breast cancer (TNBC) cells via mediating epithelial‐mesenchymal transition. Besides, OSW‐1 also could inhibit metastasis in an orthotopic model and resulted in a longer survival compared with control group. Finally, we performed RNA‐sequencing and cellular functions to investigate the molecular mechanism of how OSW‐1 inhibits TNBC, and identified NFATc2 may as a pivotal factor for OSW‐1‐mediated effects on cell death, tumor growth, invasion, and migration.

更新日期：2020-08-05

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