Aim of the study: To investigate the anti-tumor effects of Lasiokaurin on breast cancer and explore its underlying molecular mechanism./nMaterials and methods: In this study, MTT assay, plate colony formation assays, soft agar assay, and EdU assay were employed to evaluate the anti-proliferation effects of LAS. Apoptosis and cell cycle distribution were detected by flow cytometry. The molecular mechanism was predicted by performing RNA sequencing and verified by using immunoblotting assays. Breast cancer organiods derived from patient-derived xenografts model and MDA-MB-231 xenograft mouse model were established to assess the effect of LAS./nResults: Our study showed that LAS treatment significantly suppressed cell viability of 5 breast cancer cell lines, with the IC₅₀ value of approximately 1-5 μM. LAS also inhibitied the clonogenic ability and DNA synthesis of breast cancer cells, Moreover, LAS induced apoptosis and G2/M cell cycle arrest in SK-BR-3 and MDA-MB-231 cells. Notably, transcriptomic analysis predicted the mechanistic involvement of PLK1 in LAS-suppressed breast cancer progression. Our experiment data further verified that LAS reduced PLK1 mRNA and protein expression in breast cancer, accompanied by downregulating CDC25C and AKT phosphorylation. Ultimately, we confirmed that LAS inhibit breast cancer growth via inhibiting PLK1 pathway in vivo./nConclusions: Collectively, our findings revealed that LAS inhibits breast cancer progression via regulating PLK1 pathway, which provids scientific evidence for the use of traditional Chinese medicine in cancer therapy.

中文翻译：

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Lasiokaurin 调控 PLK1 诱导乳腺癌细胞 G2/M 期阻滞和凋亡

研究目的：探讨Lasiokaurin对乳腺癌的抗肿瘤作用，并探讨其潜在分子机制。/n材料与方法：本研究采用MTT法、平板集落形成法、软琼脂法、EdU法等方法进行研究。用于评估 LAS 的抗增殖作用。流式细胞术检测细胞凋亡和细胞周期分布。通过进行 RNA 测序来预测分子机制，并通过免疫印迹分析进行验证。建立源自患者异种移植模型和 MDA-MB-231 异种移植小鼠模型的乳腺癌器官来评估 LAS 的效果。/n 结果：我们的研究表明，LAS 治疗显着抑制 5 种乳腺癌细胞系的细胞活力， IC ₅₀值约为1-5 μM。LAS还抑制乳腺癌细胞的克隆形成能力和DNA合成，此外，LAS诱导SK-BR-3和MDA-MB-231细胞凋亡和G2/M细胞周期停滞。值得注意的是，转录组分析预测了 PLK1 在 LAS 抑制的乳腺癌进展中的机制参与。我们的实验数据进一步证实，LAS 降低了乳腺癌中 PLK1 mRNA 和蛋白的表达，同时下调了 CDC25C 和 AKT 磷酸化。最终，我们证实 LAS 通过抑制体内PLK1 通路来抑制乳腺癌生长。/n结论：总的来说，我们的研究结果表明LAS通过调节PLK1通路抑制乳腺癌进展，这为中药在癌症治疗中的应用提供了科学依据。