mTOR 獨(dú)立途徑下調(diào) HIF-1α 表達(dá)來抑制乳腺癌進(jìn)展

千萬不要做基因檢測合理嗎

挖掘記錄《Molecules》在.?2022 Sep 5;27(17):5716.發(fā)表了一篇題目為《Plumbagin 通過在缺氧條件下通過 PI3K/Akt/mTOR 獨(dú)立途徑下調(diào) HIF-1α 表達(dá)來抑制乳腺癌進(jìn)展》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Supawan Jampasri,?Somrudee Reabroi,?Duangjai Tungmunnithum,?Warisara Parichatikanond,?Darawan Pinthong?等完成。促進(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究內(nèi)容關(guān)鍵詞：

MCF-7細(xì)胞, PI3K/Akt/mTOR 通路,乳腺癌,缺氧誘導(dǎo)因子-1α（HIF-1α）,鉛酸

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

缺氧誘導(dǎo)因子-1α (HIF-1α) 是一種主要的轉(zhuǎn)錄調(diào)節(jié)因子，在快速生長的腫瘤的缺氧反應(yīng)中起關(guān)鍵作用。 HIF-1α的過表達(dá)與乳腺癌轉(zhuǎn)移和不良臨床預(yù)后有關(guān)。來自 Plumbago indica 的主要植物化學(xué)物質(zhì) Plumbagin 通過多種機(jī)制發(fā)揮抗癌作用。然而，它在缺氧條件下對乳腺癌細(xì)胞的確切機(jī)制從未被研究過。本研究旨在檢測白花素在常氧和低氧模擬條件下對 MCF-7 細(xì)胞活力、轉(zhuǎn)錄活性和 HIF-1α 蛋白表達(dá)的抗癌作用，并揭示潛在的信號通路。結(jié)果表明，在常氧條件下，鉛黃素降低了 MCF-7 細(xì)胞的活力，并且在暴露于氯化鈷 (CoCl2) 誘導(dǎo)的缺氧條件下觀察到更大程度的降低。在機(jī)制上，MCF-7 細(xì)胞在 CoCl2 誘導(dǎo)的缺氧條件下上調(diào)了 HIF-1α 蛋白、mRNA 和 VEGF 靶基因的表達(dá)，而這種情況被白花素處理消除了。此外，HIF-1α及其下游靶點(diǎn)的抑制不影響缺氧狀態(tài)下PI3K/Akt/mTOR通路的信號轉(zhuǎn)導(dǎo)。本研究通過在轉(zhuǎn)錄和翻譯后修飾中消除 HIF-1α，從機(jī)制上深入了解白花素在缺氧條件下對乳腺癌細(xì)胞的抗癌活性。關(guān)鍵詞：MCF-7 細(xì)胞； PI3K/Akt/mTOR 通路；乳腺癌;缺氧誘導(dǎo)因子-1α（HIF-1α）；鉛酸。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國際數(shù)據(jù)庫描述：

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.

(責(zé)任編輯：佳學(xué)基因)