研究动态
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青蒿总皂苷A通过抑制Akt/STAT3通路缓解乳腺癌细胞的糖酵解。

Saikosaponin A alleviates glycolysis of breast cancer cells through repression of Akt/STAT3 pathway.

发表日期:2023 Apr 23
作者: Yan Zhang, Kun Dai, Dedong Xu, Hua Fan, Nannan Ji, Di Wang, Yunlu Zhao, Rui Liu
来源: Cellular & Molecular Immunology

摘要:

Saikosaponin A (SSA)已被发现具有抗乳腺癌(BC)效果。然而,SSA与BC糖酵解的关联尚不清楚。我们希望探讨SSA在BC糖酵解中的作用和机制。Kaplan-Meier图示器揭示了STAT3与BC生存曲线之间的关系。通过Western blot和细胞计数试剂盒评估了蛋白激酶B(Akt)/信号转导与转录激活子3(STAT3)通路和细胞对0、5、10和15μM SSA处理的存活率。利用细胞功能实验、试剂盒和Western blot评估了用colivelin或SSA处理的BC细胞的生物学行为、乳酸和ATP含量、葡萄糖摄取和Akt/STAT3通路相关标志物。然后再次测试colivelin和SSA对BC细胞的影响。5、10和15μM SSA减弱了BC细胞中p-STAT3和p-Akt的过表达。Colivelin促进了BC细胞的存活率和增殖,并阻止了细胞凋亡,而SSA则使情况相反。同时,colivelin增强了BC细胞中乳酸和ATP含量、葡萄糖摄取和Akt/STAT3通路相关标志物水平,而SSA则是相反的。SSA对生物学行为、乳酸和ATP产生、葡萄糖摄取和Akt/STAT3通路的调节,被colivelin所挽救。我们的研究揭示了SSA作为一种有价值的减弱糖酵解的候选治疗药物,并将Akt/STAT3通路作为SSA和糖酵解调节的潜在分子靶点。 ©2023 John Wiley&Sons Ltd.
Saikosaponin A (SSA) has been revealed to have anti-breast cancer (BC) effect. However, the association between SSA and BC glycolysis is obscure. We want to probe the function and mechanism of SSA on BC glycolysis. Kaplan-Meier plotter revealed the relationship between STAT3 and the survival curve of BC. The protein kinase B (Akt)/signal transducer and activator of transcription 3 (STAT3) pathway and the viability in cells treated with or without 0, 5, 10, and 15 μM SSA were assessed by Western blot and cell counting kit-8. The biological behaviors, lactate, and ATP contents, glucose uptake, and Akt/STAT3 pathway-related markers in BC cells treated with colivelin or SSA were evaluated using cell function experiments, kit, and Western blot. Then, the impacts of colivelin and SSA on BC cells were tested again. The overexpressions of p-STAT3 and p-Akt in BC cells were weakened by 5, 10, and 15 μM SSA. Colivelin boosted the BC cell viability and proliferation and impeded apoptosis, while SSA did the opposite. Meanwhile, colivelin intensified lactate and ATP contents, glucose uptake, and Akt/STAT3 pathway-related markers level in BC cells, while SSA was the opposite. The modulation of SSA on the biological behavior, lactate and ATP productions, glucose uptake, and Akt/STAT3 pathway was rescued by colivelin. Our research unveiled new insights into SSA as a valuable candidate therapeutic agent for weakening glycolysis, and protruded the Akt/STAT3 pathway as a latent molecular target for SSA and glycolysis modulation.© 2023 John Wiley & Sons Ltd.