【佳學(xué)基因靶向藥物基因檢測】KRAS G12D 突變通過 Nrf2/CSE/H 2S 軸消除活性氧并促進(jìn)胰腺癌生長

視力檢測基因醫(yī)保報(bào)銷嗎——揭密

得知基因檢測機(jī)構(gòu)自我培訓(xùn)教材《基因組織易感位點(diǎn)列表及發(fā)生率分析》《Acta Biochim Biophys Sin (Shanghai)》在?2022 Nov 25;54(11):1-9.發(fā)表了一篇題目為《》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Kun Fan,?Shulong Zhang,?Xiaojian Ni,?Sheng Shen,?Jiwen Wang,?Wentao Sun,?Tao Suo,?Han Liu,?Xiaoling Ni,?Houbao Liu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。

腫瘤基因檢測及靶向藥物治療研究關(guān)鍵詞：

綜合性教育, KRAS突變, Nrf2;活性氧,胰腺癌。

腫瘤治療檢測基因臨床應(yīng)用結(jié)果

在胰腺癌中，KRAS G12D 可觸發(fā)胰腺癌的發(fā)生和發(fā)展。腫瘤的快速生長往往伴隨著細(xì)胞內(nèi)活性氧（ROS）的過量產(chǎn)生，這對腫瘤不利。然而，KRAS 突變胰腺癌中細(xì)胞內(nèi) ROS 水平的調(diào)節(jié)仍不清楚。在這項(xiàng)研究中，我們建立了表達(dá) KRAS 野生型 (WT) 和 G12D 突變的 BxPC3 穩(wěn)定細(xì)胞株，盡管 KRAS 突變細(xì)胞的糖酵解和增殖活力高于 KRAS WT 細(xì)胞，但發(fā)現(xiàn) ROS 水平?jīng)]有變化。關(guān)鍵的硫化氫 (H 2S) 生成酶胱硫醚-γ-裂解酶 (CSE) 在 KRAS 突變體 BxPC3 細(xì)胞中上調(diào)，其敲低顯著增加細(xì)胞內(nèi) ROS 水平并降低細(xì)胞糖酵解和增殖。核因子紅細(xì)胞 2 相關(guān)因子 2 (Nrf2) 被 KRAS 突變激活以促進(jìn) CSE 轉(zhuǎn)錄。驗(yàn)證了 CSE 啟動(dòng)子中的 Nrf2 結(jié)合位點(diǎn) (?47/?39 bp)。 CSE 過表達(dá)和在 Nrf2 敲低或 brusatol 抑制后添加 NaHS 可降低 ROS 水平并挽救細(xì)胞增殖。本研究揭示了KRAS突變胰腺癌細(xì)胞胞內(nèi)ROS水平的調(diào)控機(jī)制，為胰腺癌治療提供了潛在靶點(diǎn)。 KRAS突變； Nrf2;活性氧；胰腺癌。

腫瘤發(fā)生與革命國際數(shù)據(jù)庫描述：

In pancreatic cancer, KRAS G12D can trigger pancreatic cancer initiation and development. Rapid tumor growth is often accompanied by excess intracellular reactive oxygen species (ROS) production, which is unfavorable to tumor. However, the regulation of intracellular ROS levels in KRAS mutant pancreatic cancer remains unclear. In this study, we establish BxPC3 stable cell strains expressing KRAS wild type (WT) and G12D mutation and find unchanged ROS levels despite higher glycolysis and proliferation viability in KRAS mutant cells than KRAS WT cells. The key hydrogen sulfide (H?2S)-generating enzyme cystathionine-γ-lyase (CSE) is upregulated in KRAS mutant BxPC3 cells, and its knockdown significantly increases intracellular ROS levels and decreases cell glycolysis and proliferation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated by KRAS mutation to promote CSE transcription. An Nrf2 binding site (?47/?39 bp) in the CSE promoter is verified. CSE overexpression and the addition of NaHS after Nrf2 knockdown or inhibition by brusatol decreases ROS levels and rescues cell proliferation. Our study reveals the regulatory mechanism of intracellular ROS levels in KRAS mutant pancreatic cancer cells, which provides a potential target for pancreatic cancer therapy.Keywords:?CSE; KRAS mutation; Nrf2; ROS; pancreatic cancer.