RORα antagonist T0901317 promotes EMT in human gastric cancer MGC803 cells by RORα/β-catenin signal

Yi-Zhen ZHANG; Da-Bing PEI; Jian SU; Fang LIU; Hong XIA; Qi SU; Yi-Zhen ZHANG; Da-Bing PEI; Jian SU

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RORα antagonist T0901317 promotes EMT in human gastric cancer MGC803 cells by RORα/β-catenin signal

Author: Yi-Zhen ZHANG ¹ ; Da-Bing PEI ¹ ; Jian SU ¹ ; Fang LIU ¹ ; Hong XIA ¹ ; Qi SU ¹ ; Yi-Zhen ZHANG ² ; Da-Bing PEI ² ; Jian SU ³
Author Information

1. Hunan Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, University of South China
2. The Affiliated Hospital, Jinggangshan University
3. Hunan Clinical Research Center for Gastric Cancer Prevention and Treatment, Dept of Pathology, The Affiliated Second Hospital, University of South China
Publication Type:Journal Article
Keywords: epithelial-mesenchymal transition; human gastric cancer MGC803 cells; proliferation; RORα; RORα/β-catenin signal; T0901317
From: Chinese Pharmacological Bulletin 2023;39(4):631-637
CountryChina
Language:Chinese
Abstract: Aim To investigate the effect of RORα antagonist T0901317 promoting EMT (epithelial-mesenchymal transition) of human gastric cancer MGC803 cells by RORα/β-catenin signal. Methods Cell proliferation was detected by MTT. Cell migration and invasion were detected by cell scratch and Transwell assay respectively. RORα/β-catenin signaling molecules were detected by Western blot and immunofluorescence. RORα binding to β-catenin protein was detected by immunoprecipitation. Results MTT assay showed that the proliferation ability of T0901317 cells increased in a time-dependent manner compared with MGC803 cells (P < 0. 05). Cell scratches and Transwell experiments showed that the migration and invasion ability of T0901317 cells were significantly enhanced compared with MGC803 cells (P < 0. 05). Western blot analysis showed that RORα protein was significantly down-regulated after T0901317 compared with untreated group (P < 0. 05), and total β-catenin protein and nuclear β-catenin in MGC803 cells were up-regulated after T0901317 (P < 0. 05). Compared with the control group, RORα protein binding to β-catenin protein significantly decreased after T0901317 treatment (P < 0. 05). Compared with MGC803 cells treated with T0901317, the long spindle cells increased and the heteromorphism was more obvious. T0901317 significantly up-regulated the expression of Rac1, TGFβ1 and Vimentin in MGC803 cells (P < 0. 05), and inhibited the expression of E-cadherin (P < 0. 05). Conclusion T0901317 can promote the proliferation, migration, invasion and EMT in human gastric cancer MGC803 cells by RORα/β-catenin signal.