Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells

Chao Yan,1,* Xiaolei Song,2,* Su Wang,3 Jinhai Wang,4 Lu Li4 1Department of Radiation Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, People’s Republic of China; 2Intervention Department, Qilu Hospital (Qingdao), Cheeloo College of Medic...

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Main Authors: Yan C, Song X, Wang S, Wang J, Li L
Format: Article
Language:English
Published: Dove Medical Press 2020-11-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/knockdown-of-pdia6-inhibits-cell-proliferation-and-enhances-the-chemos-peer-reviewed-article-CMAR
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author Yan C
Song X
Wang S
Wang J
Li L
author_facet Yan C
Song X
Wang S
Wang J
Li L
author_sort Yan C
collection DOAJ
description Chao Yan,1,* Xiaolei Song,2,* Su Wang,3 Jinhai Wang,4 Lu Li4 1Department of Radiation Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, People’s Republic of China; 2Intervention Department, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, People’s Republic of China; 3Department of General Surgery, Qingdao Chengyang People’s Hospital, Qingdao 266109, People’s Republic of China; 4Gastroenterology Department, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu LiGastroenterology Department, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, People’s Republic of ChinaTel/Fax +86-29-87679290Email lilu050505@126.comBackground: Protein disulfide isomerase A6 (PDIA6), a member of the disulfide isomerase (PDI) family, has been reported to be closely associated with progression of various cancers. However, the specific effects of PDIA6 on gastric cancer (GC) remain unclear. In this study, we investigated the expression pattern and biological functions of PDIA6 in GC.Materials and Methods: The CCK-8 assay was carried out to examine cell proliferation and cisplatin cytotoxicity. The Western blot analysis was used to measure the protein expression of PDIA6, Wnt3a and β-catenin. The xenograft tumor assay was performed to evaluate the in vivo effect of PDIA6 on GC cell proliferation and chemoresistance.Results: PDIA6 was significantly elevated in GC tissues and cell lines. Down-regulation of PDIA6 inhibited GC cell proliferation and chemoresistance to cisplatin while up-regulation of PDIA6 promoted the proliferation and chemoresistance of GC cells. Besides, PDIA6 regulated the chemosensitivity of GC cells to cisplatin in vivo. Mechanically, PDIA6 served as a regulator of the Wnt/β-catenin signaling pathway by affecting the protein expression of Wnt3a and β-catenin in GC cells. Additionally, Wnt activator reversed the inhibitory effect of PDIA6 knockdown on cisplatin resistance in GC cells.Conclusion: These findings provided new insight into the potential role of PDIA6 as a promising target for drug resistance in GC chemotherapy.Keywords: PDIA6, proliferation, chemosensitivity, gastric cancer
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spelling doaj.art-1785b96bd01e493abb2380e4108566d82022-12-22T00:13:41ZengDove Medical PressCancer Management and Research1179-13222020-11-01Volume 12110511106258819Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer CellsYan CSong XWang SWang JLi LChao Yan,1,* Xiaolei Song,2,* Su Wang,3 Jinhai Wang,4 Lu Li4 1Department of Radiation Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, People’s Republic of China; 2Intervention Department, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, People’s Republic of China; 3Department of General Surgery, Qingdao Chengyang People’s Hospital, Qingdao 266109, People’s Republic of China; 4Gastroenterology Department, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu LiGastroenterology Department, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, People’s Republic of ChinaTel/Fax +86-29-87679290Email lilu050505@126.comBackground: Protein disulfide isomerase A6 (PDIA6), a member of the disulfide isomerase (PDI) family, has been reported to be closely associated with progression of various cancers. However, the specific effects of PDIA6 on gastric cancer (GC) remain unclear. In this study, we investigated the expression pattern and biological functions of PDIA6 in GC.Materials and Methods: The CCK-8 assay was carried out to examine cell proliferation and cisplatin cytotoxicity. The Western blot analysis was used to measure the protein expression of PDIA6, Wnt3a and β-catenin. The xenograft tumor assay was performed to evaluate the in vivo effect of PDIA6 on GC cell proliferation and chemoresistance.Results: PDIA6 was significantly elevated in GC tissues and cell lines. Down-regulation of PDIA6 inhibited GC cell proliferation and chemoresistance to cisplatin while up-regulation of PDIA6 promoted the proliferation and chemoresistance of GC cells. Besides, PDIA6 regulated the chemosensitivity of GC cells to cisplatin in vivo. Mechanically, PDIA6 served as a regulator of the Wnt/β-catenin signaling pathway by affecting the protein expression of Wnt3a and β-catenin in GC cells. Additionally, Wnt activator reversed the inhibitory effect of PDIA6 knockdown on cisplatin resistance in GC cells.Conclusion: These findings provided new insight into the potential role of PDIA6 as a promising target for drug resistance in GC chemotherapy.Keywords: PDIA6, proliferation, chemosensitivity, gastric cancerhttps://www.dovepress.com/knockdown-of-pdia6-inhibits-cell-proliferation-and-enhances-the-chemos-peer-reviewed-article-CMARpdia6proliferationchemosensitivitygastric cancer
spellingShingle Yan C
Song X
Wang S
Wang J
Li L
Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells
Cancer Management and Research
pdia6
proliferation
chemosensitivity
gastric cancer
title Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells
title_full Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells
title_fullStr Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells
title_full_unstemmed Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells
title_short Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells
title_sort knockdown of pdia6 inhibits cell proliferation and enhances the chemosensitivity in gastric cancer cells
topic pdia6
proliferation
chemosensitivity
gastric cancer
url https://www.dovepress.com/knockdown-of-pdia6-inhibits-cell-proliferation-and-enhances-the-chemos-peer-reviewed-article-CMAR
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