敲低微粒体谷胱甘肽 S-转移酶 1 抑制肺腺癌细胞增殖并诱导细胞凋亡。

Knockdown of microsomal glutathione S-transferase 1 inhibits lung adenocarcinoma cell proliferation and induces apoptosis.

机构信息

Department of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 650118, China; Department of Yunnan Tumor Research Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 650118, China; Department of Anatomy, Guangdong Provincial Key Laboratory of Medical Biomechanics, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China.

Department of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 650118, China.

出版信息

Biomed Pharmacother. 2020 Jan;121:109562. doi: 10.1016/j.biopha.2019.109562. Epub 2019 Nov 7.

DOI:10.1016/j.biopha.2019.109562

PMID:31707341

Abstract

BACKGROUND

Lung cancer has been the most common cancer worldwide. Microsomal glutathione S-transferase 1 (MGST1) has been reported to play vital roles in oxidative stress, tumor occurrence and drug resistance. However, the biological function and molecular mechanism of MGST1 in lung adenocarcinoma (LUAD) has not yet been elucidated.

METHODS

The expression of MGST1 in LUAD tissues and cell lines was evaluated by immunohistochemistry and western blotting, respectively. MGST1 was knocked down by shRNA lentivirus. Cell proliferation was evaluated by MTS, colony formation and EdU assays. Apoptosis was detected by flow cytometry. The potential molecules involved in cell proliferation and apoptosis were examined by western blotting. Finally, the effect of MGST1 on tumor growth in vivo was evaluated in a nude mouse xenograft model.

RESULTS

TCGA database analysis and immunohistochemistry demonstrated that MGST1 was highly expressed in LUAD tissues. MGST1 expression in LUAD was correlated with AJCC stage and poor overall survival of patients. MGST1 knockdown significantly inhibited LUAD cell proliferation and induced apoptosis. Mechanistic analyses revealed that MGST1 knockdown might inhibit cell proliferation by inactivating the AKT/GSK-3β pathway signaling and promote cell apoptosis by regulating the mitochondrial apoptosis pathway related proteins. Moreover, knockdown of MGST1 suppressed tumor growth in vivo.

CONCLUSIONS

MGST1 plays an important role in LUAD tumorigenesis and might serve as a potential prognostic factor and therapeutic target in LUAD.

摘要

背景

肺癌是全球最常见的癌症。微粒体谷胱甘肽 S-转移酶 1（MGST1）已被报道在氧化应激、肿瘤发生和耐药性中发挥重要作用。然而，MGST1 在肺腺癌（LUAD）中的生物学功能和分子机制尚未阐明。

方法

通过免疫组织化学和 Western blot 分别评估 LUAD 组织和细胞系中 MGST1 的表达。用 shRNA 慢病毒敲低 MGST1。通过 MTS、集落形成和 EdU 测定评估细胞增殖。通过流式细胞术检测细胞凋亡。通过 Western blot 检测参与细胞增殖和凋亡的潜在分子。最后，在裸鼠异种移植模型中评估 MGST1 对肿瘤生长的影响。

结果

TCGA 数据库分析和免疫组化表明，MGST1 在 LUAD 组织中高表达。LUAD 中 MGST1 的表达与 AJCC 分期和患者的总体生存率差相关。MGST1 敲低显著抑制 LUAD 细胞增殖并诱导细胞凋亡。机制分析表明，MGST1 敲低可能通过失活 AKT/GSK-3β 通路信号来抑制细胞增殖，并通过调节线粒体凋亡通路相关蛋白来促进细胞凋亡。此外，MGST1 的敲低抑制了体内肿瘤的生长。