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Exosome-Delivered c-Met siRNA Could Reverse Chemoresistance to Cisplatin in Gastric Cancer

Authors Zhang Q, Zhang H, Ning T, Liu D, Deng T, Liu R, Bai M, Zhu K, Li J, Fan Q, Ying G, Ba Y

Received 16 September 2019

Accepted for publication 10 January 2020

Published 1 April 2020 Volume 2020:15 Pages 2323—2335

DOI https://doi.org/10.2147/IJN.S231214

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Qiumo Zhang,1,* Haiyang Zhang,1,* Tao Ning,1 Dongying Liu,1 Ting Deng,1 Rui Liu,1 Ming Bai,1 Kegan Zhu,1 Jialu Li,2 Qian Fan,1 Guoguang Ying,1 Yi Ba1

1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China; 2Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai 200001, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yi Ba; Guoguang Ying
Email yingguoguang163@163.com; bayi@tjmuch.com

Background: Drug resistance often occurs in the treatment of gastric cancer, which is the main cause of poor prognosis of chemotherapy. c-Met is overexpressed in a variety of tumors including gastric cancer, often leads to poor prognosis of gastric cancer, therefore regarded as a key target for the treatment of gastric cancer. This study aims to determine whether exosomes with si-c-Met could inhibit the resistance to cisplatin in gastric cancer (GC).
Methods: The protein expression levels of c-Met in tumor tissues and normal tissues of patients were evaluated by Western blot (WB) and immunohistochemistry (IHC), HEK293T cells were transfected with si-c-Met, exosomes were isolated, then co-cultured with gastric cancer cell lines and confirmed that it was incorporated into the cells by transmitted electron microscopy. Functional experiments were performed to examine the inhibitory effect of exo-si-c-Met on gastric cancer cell resistance in vitro, and xenograft models were used to reveal that exo-si-c-Met can enhance the sensitivity of tumors to cisplatin in vivo.
Results: High expression of c-Met is associated with poor prognosis of GC patients. si-c-Met significantly inhibited migration, invasion and promoted apoptosis in vitro, which indicated that si-c-Met sensitizes the response of gastric cancer cells to cisplatin. Exo-si-c-Met sharply reduced c-Met expression in gastric cancer cells and reverse the resistance to cisplatin in vitro and in vivo.
Conclusion: Our results indicate that exo-si-c-Met can inhibit the invasion and migration of gastric cancer cells and promote apoptosis in vitro and inhibit tumor growth in vivo, reversing the resistance to cisplatin in gastric cancer.

Keywords: exosomes, c-Met, siRNA, chemoresistance, gastric cancer

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