Back to Journals » OncoTargets and Therapy » Volume 11

RACK1 induces chemotherapy resistance in esophageal carcinoma by upregulating the PI3K/AKT pathway and Bcl-2 expression

Authors Liu B, Wang C, Chen P, Cheng B, Cheng Y

Received 28 September 2017

Accepted for publication 28 November 2017

Published 4 January 2018 Volume 2018:11 Pages 211—220

DOI https://doi.org/10.2147/OTT.S152818

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Federico Perche

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza


Bowen Liu,1 Cong Wang,1 Pengxiang Chen,1 Bo Cheng,2 Yufeng Cheng1

1Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Provincial Cancer Hospital, Jinan, Shandong, People’s Republic of China

Introduction: Accumulating evidence indicates that RACK1 is involved in the progression of tumors. We aimed to evaluate the function of RACK1 in esophageal squamous cell carcinoma (ESCC) and its role in the mechanism of chemotherapy resistance.
Materials and methods: Transfected ESCC cell lines with plasmids expressed shRACK1 or open reading frame (ORF) targeting RACK1 and established stable cell lines. We then examined the effects of RACK1 on cell proliferation and chemotherapy resistance in ESCC cell lines, and the expression of AKT, pAKT, ERK1/2, Bcl-2, and Bim was introduced to further detect the association between RACK1 and chemotherapy resistance.
Results:
The proliferation ability of ESCC cells was improved in the overexpression RACK1 groups (P<0.001) and decreased in the transfected shRACK1 groups (P<0.001) compared with the control ones. Meanwhile, upregulation of RACK1 significantly suppressed cisplatin-induced apoptosis in Eca109 and EC9706 cells, while downregulation of RACK1 promoted the sensitivity compared to the control group (Eca109: P<0.001 for shRACK1, P<0.01 for shNC, and P<0.001 for overexpression group; EC9706: P<0.001 for shRACK1, P<0.001 for shNC, and P<0.05 for overexpression group). Furthermore, we found that RACK1 could activate the PI3K/AKT pathway and increase the expression level of Bcl-2 in ESCC, which leads to the enhancement of chemoresistance in ESCC.
Conclusion: RACK1 promotes proliferation and chemotherapy resistance in ESCC by activating the PI3K/AKT pathway and upregulating the Bcl-2 expression.

Keywords: RACK1, ESCC, chemotherapy resistance, PI3K/AKT pathway, Bcl-2

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]