Emodin sensitizes human pancreatic cancer cells to EGFR inhibitor through suppressing Stat3 signaling pathway
Received 4 July 2019
Accepted for publication 28 August 2019
Published 17 September 2019 Volume 2019:11 Pages 8463—8473
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Eileen O'Reilly
Zhaohong Wang,1,2,* Hui Chen,1,* Jingjing Chen,1,* Zhong Hong,1 Yi Liao,1 Qiyu Zhang,1,2 Hongfei Tong1
1Department of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qiyu Zhang; Hongfei Tong
Department of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan W Road, Lucheng Qu, Wenzhou Shi, Zhejiang Sheng 32500, People’s Republic of China
Tel +86 5 778 800 2710; +86 5 778 800 2710
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Background: Excessive expression of EGFR is closely related to tumor formation, transfer and deterioration, which has attracted much attention. EGFR overexpression may be detected in up to 90% of pancreatic tumors. However, drug resistance of EGFR inhibitors targeting treatment severely limits its clinical application.
Methods: In this study, Western blotting was used to detect the expression of p-Stat3, EGFR, Bcl-2, cleaved-caspase3 and Bax. Cell apoptosis was evaluated via flow cytometry. The colon assay and MTT assay were applied for detecting the cell proliferation in vitro. The xenograft mouse model was used to examine the cell proliferation in vivo.
Results: Emodin remarkably enhanced the anti-cancer effect of EGFR inhibitor on pancreatic cancer cells. In addition, emodin promoted afatinib-induced apoptosis by inhibiting the Stat3 signaling pathway. Meanwhile, siRNAs against Stat3 significantly increased the apoptosis of pancreatic cancer cells. EGFR inhibitor promoted phosphorylation of Stat3 in pancreatic cancer cells. Interestingly, emodin combined with EGFR inhibitor inhibited the proliferation of pancreatic cancer cells in vitro. The tumor xenograft mice model was further confirmed that emodin possessed a synergy anticancer effect with afatinib on pancreatic cancer cells by regulating the Stat3 expression.
Conclusion: These results indicate that the combination of emodin with EGFR inhibitor is an effective therapeutic strategy to sensitize human pancreatic cancer.
Keywords: pancreatic cancer, EGFR inhibitors, afatinib, Stat3
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