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

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

  • Biomed Pharmacother. 2020 Jan;121:109562. doi: 10.1016/j.biopha.2019.109562.
Baozhen Zeng 1,  Chunlei Ge 2,  Ruilei Li 2,  Zhiwei Zhang 3,  Qiaofen Fu 2,  Zhen Li 2,  Zhuying Lin 2,  Lin Liu 4,  Yuanbo Xue 2,  Yuanyuan Xu 2,  Juan He 2,  Huan Guo 2,  Chunyan Li 2,  Wenhua Huang 5,  Xin Song 6,  Youguang Huang 7
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 650118, China.
  • 3 Department of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 650118, China; Department of Oncology, Affiliated Hospital of Hebei University of Engineering, Handan, Hebei, 056002, China.
  • 4 Puer Traditional Ethnomedicine Institute, Puer, 665000, China.
  • 5 Department of Anatomy, Guangdong Provincial Key Laboratory of Medical Biomechanics, School of Basic Medical Science, Southern Medical University, Guangzhou, 510515, China. Electronic address: huangwenhua2009@139.com.
  • 6 Department of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 650118, China. Electronic address: songxin_68@126.com.
  • 7 Department of Yunnan Tumor Research Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 650118, China. Electronic address: huangyouguang2008@126.com.
PMID: 31707341 DOI: 10.1016/j.biopha.2019.109562
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.

Keywords

AKT/GSK-3β; Apoptosis; Lung adenocarcinoma; Microsomal glutathione transferase-1; Proliferation.

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