文章：

靶向肝细胞癌生长：Haprolid通过下调DExH-Box解旋酶9抑制AKT信号通路

Targeting Hepatocellular Carcinoma Growth: Haprolid’s Inhibition of AKT Signaling Through DExH-Box Helicase 9 Downregulation

原文发布日期：28 January 2025

DOI: 10.3390/cancers17030443

类型: Article

开放获取: 是

英文摘要：

Objective:Haprolid, a novel compound extracted from Myxobacterium, has been proven to possess selective toxicity towards various tumor cells, effectively inhibiting the growth of hepatocellular carcinoma (HCC). However, the underlying molecular mechanism remains unclear.Methods:To identify differentially expressed proteins (DEPs), isobaric tags for relative and absolute quantitation (iTRAQ) were employed. The clinical significance of DExH-Box Helicase 9 (DHX9) was determined using tissue microarrays in HCC patients. Changes in protein expression were detected using Western blotting, qPCR, and immunohistochemistry. Cell proliferation was evaluated using CCK-8 and crystal violet staining. Cell apoptosis was assessed using Alexa Fluor 647 Annexin V. Xenograft tumor experiments were conducted in animals.Results:iTRAQ screening identified DHX9 as a DEP. DHX9 was discovered to be highly expressed in HCC tissues, correlating with poor prognosis in patients. Haprolid downregulated DHX9 expression, while knockdown of DHX9 suppressed HCC cell proliferation and migration and promoted apoptosis. Meanwhile, overexpression of DHX9 mitigated the inhibitory effect of Haprolid on HCC cells. Knockdown of DHX9 inhibited the AKT signaling pathway, and SC79 reversed the inhibitory effect of DHX9 knockdown on HCC cells. Xenograft experiments confirmed that the knockdown of DHX9 inhibited HCC growth, while the overexpression of DHX9 attenuated the inhibitory effect of Haprolid on HCC growth.Conclusions:Haprolid inhibits the AKT signaling pathway by downregulating DHX9, ultimately suppressing HCC growth. This finding opens up new avenues for targeted HCC therapy.

摘要翻译： 

目的：Haprolid是一种从粘细菌中提取的新型化合物，已被证实对多种肿瘤细胞具有选择性毒性，能有效抑制肝细胞癌（HCC）的生长，但其具体分子机制尚不明确。 方法：采用同位素标记相对和绝对定量（iTRAQ）技术筛选差异表达蛋白（DEPs）。通过组织微阵列分析DExH-Box解旋酶9（DHX9）在HCC患者中的临床意义。利用蛋白质印迹法、定量聚合酶链反应和免疫组织化学检测蛋白表达变化。采用CCK-8法和结晶紫染色评估细胞增殖能力，通过Alexa Fluor 647标记的膜联蛋白V检测细胞凋亡情况，并在动物体内进行异种移植瘤实验。 结果：iTRAQ筛选结果显示DHX9为差异表达蛋白。研究发现DHX9在HCC组织中高表达，且与患者不良预后相关。Haprolid能下调DHX9表达，而敲低DHX9可抑制HCC细胞增殖与迁移并促进细胞凋亡。同时，过表达DHX9能减弱Haprolid对HCC细胞的抑制作用。敲低DHX9可抑制AKT信号通路，而SC79能逆转DHX9敲低对HCC细胞的抑制效应。动物实验证实，敲低DHX9可抑制HCC生长，而过表达DHX9则会削弱Haprolid对HCC生长的抑制作用。 结论：Haprolid通过下调DHX9抑制AKT信号通路，最终遏制HCC生长。这一发现为肝细胞癌的靶向治疗开辟了新途径。

原文链接：

Targeting Hepatocellular Carcinoma Growth: Haprolid’s Inhibition of AKT Signaling Through DExH-Box Helicase 9 Downregulation