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MEOX2 的过表达通过抑制喉癌细胞中的 PI3K/Akt 通路促进细胞凋亡。

Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Guizhou Medical University, Wuhan, China.

出版信息

Neoplasma. 2018 Sep 19;65(5):745-752. doi: 10.4149/neo_2018_171218N824. Epub 2018 Jun 18.

Abstract

The early-stage diagnosis and treatment for the recurrence of larynx carcinoma needs further investigation. Mesenchyme homeobox 2 (MEOX2) was speculated as a novel suppressor gene in larynx carcinoma in our study, the molecular mechanism was studied. Real-time quantitative PCR (RT-qPCR) and Western blot were used to detect mRNA and protein levels of MEOX2 in laryngeal cancer tissues and cells (Hep-2, TU212, AMC-NH-8 and TU686 cells), and also apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase (Akt) related factors in TU212 cells transfected with MEOX2. Cell counting kit-8 (CCK8) assay and Annexin-Ⅴ/PI staining assay were conducted to determine cell viability and apoptosis rates respectively.46 patients with larynx carcinoma were involved in this study. The expression of MEOX2 was lower in larynx carcinoma tissues than normal tissues, correlated with clinical stages, differentiated degrees, and survival times. The expression of MEOX2 was the lowest among those laryngeal cancer cells, and was chosen to be transfected with MEOX2 in the following study. Over-expression of MEOX2 inhibited cell viability and promoted apoptosis of TU212 cells, via increasing the expression levels of Caspase-3, and decreasing levels of C-Myc, XIAP, PI3K p110α, PI3K p110β, PI3K class III and p-Akt. In summary, the expression levels of MEOX2 were inhibited in larynx carcinoma than normal tissues, correlated with the progression of the cancer. Over-expression of MEOX2 in laryngeal cancer cells inhibited cell viability and promoted apoptosis, via regulating apoptosis and PI3K/Akt pathway related factors. It would provide evidence for MEOX2 to be used as a therapeutical gene in larynx carcinoma.

摘要

喉癌复发的早期诊断和治疗需要进一步研究。本研究推测间叶同源盒 2(MEOX2)是喉癌的一种新的抑制基因,研究其分子机制。实时定量 PCR(RT-qPCR)和 Western blot 用于检测喉癌组织和细胞(Hep-2、TU212、AMC-NH-8 和 TU686 细胞)中 MEOX2 的 mRNA 和蛋白水平,以及转染 MEOX2 的 TU212 细胞中凋亡和磷酸肌醇 3-激酶(PI3K)/蛋白激酶(Akt)相关因子。细胞计数试剂盒-8(CCK8)测定和 Annexin-Ⅴ/PI 染色测定分别用于确定细胞活力和凋亡率。本研究共纳入 46 例喉癌患者。MEOX2 在喉癌组织中的表达低于正常组织,与临床分期、分化程度和生存时间有关。在这些喉癌细胞中,MEOX2 的表达最低,因此选择在后续研究中转染 MEOX2。过表达 MEOX2 通过增加 Caspase-3 的表达水平和降低 C-Myc、XIAP、PI3K p110α、PI3K p110β、PI3K Ⅲ类和 p-Akt 的水平,抑制 TU212 细胞的活力并促进其凋亡。总之,MEOX2 在喉癌组织中的表达低于正常组织,与癌症的进展有关。在喉癌细胞中过表达 MEOX2 通过调节凋亡和 PI3K/Akt 通路相关因子抑制细胞活力并促进凋亡。这为将 MEOX2 用作喉癌的治疗基因提供了依据。

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