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Mefloquine Inhibited Esophageal Squamous Cells Carcinoma Proliferation by Induction of Mitochondrial Autophagy

41 Pages Posted: 2 Aug 2019

See all articles by Yifei Xie

Yifei Xie

Zhengzhou University - Department of Pathophysiology

Jing Zhang

Zhengzhou University - Department of Pathophysiology

Jimin Zhao

Zhengzhou University - Department of Pathophysiology

Xianyu Lu

Zhengzhou University - Department of Pathophysiology

Yaxing Wei

Zhengzhou University - Department of Pathophysiology

Bo Li

Zhengzhou University - Department of Pathophysiology

Zhuo Bao

Zhengzhou University - Department of Pathophysiology

Qiang Yuan

Zhengzhou University - Department of Pathophysiology

Xinhuan Chen

Zhengzhou University - Department of Pathophysiology

Zigang Dong

University of Minnesota - Austin - The Hormel Institute; University of Minnesota - Minneapolis - Program in Bioinformatics and Computational Biology; China-US (Henan) Hormel Cancer Institute

Kangdong Liu

China-US (Henan) Hormel Cancer Institute

More...

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) still has high rates of incidence and mortality, despite developments in medical technology. Therefore, looking for cancer treatment drugs with high efficiency and low toxicity remains very important. In the previous study, we screened FDA-approved drugs, approved for uses other than tumor treatment, and found that mefloquine (MQ), which is used for prevention and treatment of malaria, inhibited clone formation of ESCC cells.

Methods: Proteomics and mass spectrometry (MS) were applied to profile proteome changes in ESCC cells after MQ treatment. KEGG was performed to analyse the significantly down-regulated pathways and proteins. Electron microscopy was used to observe mitochondrial changes in MQ-treated KYSE150 cells. And patient derived xenograft (PDX) mouse model was used to observe the anti-tumor effect of MQ in vivo.

Findings: MS analyse showed that various proteins changed in MQ-treated KYSE150 cells. KEGG analyse identified dysregulated pathways and proteins. Among these proteins, SDHC, SDHD, MTCO3 and NDUFV3, all known to be essential enzymes in the mitochondrial respiration chain, were involved in these pathways and were notably down-regulated in MQ-treated cells. Meanwhile, mitochondrial autophagy was verified in MQ-treated cells by electron microscopy. Furthermore, MQ significantly inhibited tumor growth in a patient-derived xenograft mouse model of ESCC. All considered, MQ suppressed ESCC cell proliferation by induction of mitochondrial autophagy.

Interpretation: Our data suggested that MQ may be a promising drug for ESCC treatment and chemoprevention.

Funding Statement: This work was supported by grants from the National Natural Science Foundations of China (No. 81872335, 81572812, and 81472324) and the Natural Science Foundations of Henan (No. 161100510300).

Declaration of Interests: The authors declare no conflicts of interest.

Ethics Approval Statement: All procedures involving animals in this study were approved by the Animal Ethics Committee.

Keywords: Esophageal squamous cell carcinoma (ESCC); Mefloquine (MQ); Mitochondrial autophagy

Suggested Citation

Xie, Yifei and Zhang, Jing and Zhao, Jimin and Lu, Xianyu and Wei, Yaxing and Li, Bo and Bao, Zhuo and Yuan, Qiang and Chen, Xinhuan and Dong, Zigang and Liu, Kangdong, Mefloquine Inhibited Esophageal Squamous Cells Carcinoma Proliferation by Induction of Mitochondrial Autophagy (July 31, 2019). Available at SSRN: https://ssrn.com/abstract=3429885 or http://dx.doi.org/10.2139/ssrn.3429885

Yifei Xie

Zhengzhou University - Department of Pathophysiology

China

Jing Zhang

Zhengzhou University - Department of Pathophysiology

China

Jimin Zhao

Zhengzhou University - Department of Pathophysiology

China

Xianyu Lu

Zhengzhou University - Department of Pathophysiology

China

Yaxing Wei

Zhengzhou University - Department of Pathophysiology

China

Bo Li

Zhengzhou University - Department of Pathophysiology

China

Zhuo Bao

Zhengzhou University - Department of Pathophysiology

China

Qiang Yuan

Zhengzhou University - Department of Pathophysiology

China

Xinhuan Chen

Zhengzhou University - Department of Pathophysiology

China

Zigang Dong

University of Minnesota - Austin - The Hormel Institute ( email )

Austin, MN
United States

University of Minnesota - Minneapolis - Program in Bioinformatics and Computational Biology ( email )

Minneapolis, MN
United States

China-US (Henan) Hormel Cancer Institute ( email )

China

Kangdong Liu (Contact Author)

China-US (Henan) Hormel Cancer Institute ( email )

China

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