【佳学基因靶向药物基因检测】KRAS G12D 突变通过 Nrf2/CSE/H 2S 轴消除活性氧并促进胰腺癌生长

视力检测基因医保报销吗——揭密

得知基因检测机构自我培训教材《基因组织易感位点列表及发生率分析》《Acta Biochim Biophys Sin (Shanghai)》在 2022 Nov 25;54(11):1-9.发表了一篇题目为《》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Kun Fan, Shulong Zhang, Xiaojian Ni, Sheng Shen, Jiwen Wang, Wentao Sun, Tao Suo, Han Liu, Xiaoling Ni, Houbao Liu等完成。促进了肿瘤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。

肿瘤基因检测及靶向药物治疗研究关键词：

综合性教育, KRAS突变, Nrf2;活性氧,胰腺癌。

肿瘤治疗检测基因临床应用结果

在胰腺癌中，KRAS G12D 可触发胰腺癌的发生和发展。肿瘤的快速生长往往伴随着细胞内活性氧（ROS）的过量产生，这对肿瘤不利。然而，KRAS 突变胰腺癌中细胞内 ROS 水平的调节仍不清楚。在这项研究中，我们建立了表达 KRAS 野生型 (WT) 和 G12D 突变的 BxPC3 稳定细胞株，尽管 KRAS 突变细胞的糖酵解和增殖活力高于 KRAS WT 细胞，但发现 ROS 水平没有变化。关键的硫化氢 (H 2S) 生成酶胱硫醚-γ-裂解酶 (CSE) 在 KRAS 突变体 BxPC3 细胞中上调，其敲低显着增加细胞内 ROS 水平并降低细胞糖酵解和增殖。核因子红细胞 2 相关因子 2 (Nrf2) 被 KRAS 突变激活以促进 CSE 转录。验证了 CSE 启动子中的 Nrf2 结合位点 (‒47/‒39 bp)。 CSE 过表达和在 Nrf2 敲低或 brusatol 抑制后添加 NaHS 可降低 ROS 水平并挽救细胞增殖。本研究揭示了KRAS突变胰腺癌细胞胞内ROS水平的调控机制，为胰腺癌治疗提供了潜在靶点。 KRAS突变； Nrf2;活性氧；胰腺癌。

肿瘤发生与革命国际数据库描述：

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.