mTOR 独立途径下调 HIF-1α 表达来抑制乳腺癌进展

千万不要做基因检测合理吗

挖掘记录《Molecules》在. 2022 Sep 5;27(17):5716.发表了一篇题目为《Plumbagin 通过在缺氧条件下通过 PI3K/Akt/mTOR 独立途径下调 HIF-1α 表达来抑制乳腺癌进展》dota2吧雷电竞 dota2吧雷电竞治疗基因检测临床研究文章。该研究由Supawan Jampasri, Somrudee Reabroi, Duangjai Tungmunnithum, Warisara Parichatikanond, Darawan Pinthong 等完成。促进了dota2吧雷电竞的正确治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及正确治疗临床研究内容关键词：

MCF-7细胞, PI3K/Akt/mTOR 通路,乳腺癌,缺氧诱导因子-1α（HIF-1α）,铅酸

肿瘤靶向治疗基因检测临床应用结果

缺氧诱导因子-1α (HIF-1α) 是一种主要的转录调节因子，在快速生长的肿瘤的缺氧反应中起关键作用。 HIF-1α的过表达与乳腺癌转移和不良临床预后有关。来自 Plumbago indica 的主要植物化学物质 Plumbagin 通过多种机制发挥抗癌作用。然而，它在缺氧条件下对乳腺癌细胞的确切机制从未被研究过。本研究旨在检测白花素在常氧和低氧模拟条件下对 MCF-7 细胞活力、转录活性和 HIF-1α 蛋白表达的抗癌作用，并揭示潜在的信号通路。结果表明，在常氧条件下，铅黄素降低了 MCF-7 细胞的活力，并且在暴露于氯化钴 (CoCl2) 诱导的缺氧条件下观察到更大程度的降低。在机制上，MCF-7 细胞在 CoCl2 诱导的缺氧条件下上调了 HIF-1α 蛋白、mRNA 和 VEGF 靶基因的表达，而这种情况被白花素处理消除了。此外，HIF-1α及其下游靶点的抑制不影响缺氧状态下PI3K/Akt/mTOR通路的信号转导。本研究通过在转录和翻译后修饰中消除 HIF-1α，从机制上深入了解白花素在缺氧条件下对乳腺癌细胞的抗癌活性。关键词：MCF-7 细胞； PI3K/Akt/mTOR 通路；乳腺癌;缺氧诱导因子-1α（HIF-1α）；铅酸。

肿瘤发生与反复转移国际数据库描述：

Hypoxia-inducible factor-1α (HIF-1α) is a major transcriptional regulator that plays a crucial role in the hypoxic response of rapidly growing tumors. Overexpression of HIF-1α has been associated with breast cancer metastasis and poor clinical prognosis. Plumbagin, the main phytochemical from Plumbago indica, exerts anticancer effects via multiple mechanisms. However, its precise mechanisms on breast cancer cells under hypoxic conditions has never been investigated. This study aims to examine the anticancer effect of plumbagin on MCF-7 cell viability, transcriptional activity, and protein expression of HIF-1α under normoxia and hypoxia-mimicking conditions, as well as reveal the underlying signaling pathways. The results demonstrate that plumbagin decreased MCF-7 cell viability under normoxic conditions, and a greater extent of reduction was observed upon exposure to hypoxic conditions induced by cobalt chloride (CoCl2). Mechanistically, MCF-7 cells upregulated the expression of HIF-1α protein, mRNA, and the VEGF target gene under CoCl2-induced hypoxia, which were abolished by plumbagin treatment. In addition, inhibition of HIF-1α and its downstream targets did not affect the signaling transduction of the PI3K/Akt/mTOR pathway under hypoxic state. This study provides mechanistic insight into the anticancer activity of plumbagin in breast cancer cells under hypoxic conditions by abolishing HIF-1α at transcription and post-translational modifications.Keywords: MCF-7 cells; PI3K/Akt/mTOR pathway; breast cancer; hypoxia-inducible factor-1α (HIF-1α); plumbagin.

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