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BATF2 reverses multidrug resistance of human gastric cancer cells by suppressing Wnt/β-catenin signaling

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Abstract

Gastric cancer (GC) is a commonly occurring neoplasm worldwide. The occurrence of multidrug resistance (MDR) in GC cells is the main obstacle to effective GC chemotherapy. The aim of the present study was to reveal the functional role and the underlying mechanisms of basic leucine zipper ATF-like transcription factor 2 (BATF2), a novel tumor suppressor, on MDR in GC cells. Here, we first found that SGC7901/VCR and SGC7901/ADR cells had higher drug resistance than SGC7901 cells using methylthiazol tetrazolium (MTT) and flow cytometry analysis. Moreover, MDR-related proteins and Wnt/β-catenin pathway markers were all upregulated in SGC7901/VCR cells compared to SGC7901 cells by quantitative reverse transcription-PCR (qRT-PCR) and western blot analyses. Subsequently, we observed BATF2 was downregulated in SGC7901/VCR cells and BATF2 overexpression significantly induced cell cycle G0/G1 phase arrest and apoptosis. Furthermore, overexpression of BATF2 could suppress Wnt/β-catenin signaling and increase drug susceptibility by downregulating Wnt/β-catenin pathway markers. In addition, knockdown of β-catenin imitated the effects of BATF2 overexpression on drug susceptibility. Importantly, enhancing the Wnt/β-catenin pathway could reverse the inhibitory effects of BATF2 on MDR. In conclusion, BATF2 was downregulated in MDR GC cells and overexpression of BATF2 could reverse the MDR of GC cells by inactivating the Wnt/β-catenin pathway.

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Acknowledgements

This study was supported by the applied Basic Research Joint Fund Project of Yunnan Provincial Science and Technology Department-Kunming Medical University (Grant No. 2017FE468(-108), 2015FB099) and Scientific Research Fund Project of Yunnan Provincial Education Department (Grant No. 2016ZDX020).

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Authors and Affiliations

  1. Second Department of General Surgery, the First People’s Hospital of Yunnan Province, No. 157 Jinbi Road, Kunming, 650032, Yunnan Province, China

    Wei Yang, Bian Wu, Ning Ma, Yongfang Wang, Jianhui Guo, Jun Zhu & Sihui Zhao

  2. The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Kunming, 650032, Yunnan Province, China

    Wei Yang, Bian Wu, Ning Ma, Yongfang Wang, Jianhui Guo, Jun Zhu & Sihui Zhao

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  1. Wei Yang
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  2. Bian Wu
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Correspondence to Sihui Zhao.

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Editor: Tetsuji Okamoto

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Yang, W., Wu, B., Ma, N. et al. BATF2 reverses multidrug resistance of human gastric cancer cells by suppressing Wnt/β-catenin signaling. In Vitro Cell.Dev.Biol.-Animal 55, 445–452 (2019). https://doi.org/10.1007/s11626-019-00360-5

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