2. Academic Validation
  3. DHRS2 mediates cell growth inhibition induced by Trichothecin in nasopharyngeal carcinoma

DHRS2 mediates cell growth inhibition induced by Trichothecin in nasopharyngeal carcinoma

  • J Exp Clin Cancer Res. 2019 Jul 10;38(1):300. doi: 10.1186/s13046-019-1301-1.
Xiangjian Luo 1 2 3 4,  Namei Li 5 6 7,  Xu Zhao 5 6 7,  Chaoliang Liao 5 6 7,  Runxin Ye 5 6 7,  Can Cheng 5 6 7,  Zhijie Xu 8,  Jing Quan 5 6 7,  Jikai Liu 9,  Ya Cao 5 6 7 10
Affiliations

Affiliations

  • 1 Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, People's Republic of China. luocsu@hotmail.com.
  • 2 Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, People's Republic of China. luocsu@hotmail.com.
  • 3 Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, 410078, Hunan, China. luocsu@hotmail.com.
  • 4 Molecular Imaging Research Center of Central South University, Changsha, 410078, Hunan, China. luocsu@hotmail.com.
  • 5 Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, People's Republic of China.
  • 6 Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, People's Republic of China.
  • 7 Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, 410078, Hunan, China.
  • 8 Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410078, Hunan, China.
  • 9 School of Pharmacy, South-central University for Nationalities, Wuhan, 430074, Hubei, China.
  • 10 Molecular Imaging Research Center of Central South University, Changsha, 410078, Hunan, China.
PMID: 31291971 DOI: 10.1186/s13046-019-1301-1
Abstract

Background: Cancer is fundamentally a deregulation of cell growth and proliferation. Cancer cells often have perturbed metabolism that leads to the alteration of metabolic intermediates. Dehydrogenase/reductase member 2 (DHRS2) belongs to short-chain alcohol dehydrogenase/reductase (SDR) superfamily, which is functionally involved in a number of intermediary metabolic processes and in the metabolism of lipid signaling molecules. DHRS2 displays closely association with the inhibition of cell proliferation, migration and quiescence in cancers.

Methods: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium (MTS), 5-ethynyl-2'-deoxyuridine (EdU) and colony formation assays were applied to evaluate the proliferative ability of nasopharyngeal carcinoma (NPC) cells. We performed lipid metabolite profiling using gas chromatography coupled with mass spectrometry (GC/MS) to identify the proximal metabolite changes linked to DHRS2 overexpression. RNA Sequencing technique combined with differentially expressed genes analysis was applied to identify the expression of genes responsible for the anti-tumor effect of trichothecin (TCN), a natural sesquiterpenoid compound isolated from an endophytic fungus.

Results: Our current findings reveal that DHRS2 affects lipid metabolite profiling to induce cell cycle arrest and growth inhibition in NPC cells. Furthermore, we demonstrate that TCN is able to induce growth inhibition of NPC in vitro and in vivo by up-regulating DHRS2.

Conclusions: Our report suggests that activating DHRS2 to reprogram lipid homeostasis may be a target for the development of targeted therapies against NPC. Moreover, TCN could be exploited for therapeutic gain against NPC by targeting DHRS2 and it may also be developed as a tool to enhance understanding the biological function of DHRS2.

Keywords

Cell cycle; DHRS2; Lipid metabolism; Nasopharyngeal carcinoma; Trichothecin.

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