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CLC number: R945

On-line Access: 2020-03-05

Received: 2019-08-02

Revision Accepted: 2019-10-24

Crosschecked: 2020-02-22

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Citations:  Bibtex RefMan EndNote GB/T7714


Fu-Qiang Hu


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Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.3 P.218-233


Inhibition of chemotherapy-related breast tumor EMT by application of redox-sensitive siRNA delivery system CSO-ss-SA/siRNA along with doxorubicin treatment

Author(s):  Xuan Liu, Xue-Qing Zhou, Xu-Wei Shang, Li Wang, Yi Li, Hong Yuan, Fu-Qiang Hu

Affiliation(s):  College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China

Corresponding email(s):   hufq@zju.edu.cn

Key Words:  Doxorubicin, Tumor metastasis, Ras-related C3 botulinum toxin substrate 1 (RAC1), Epithelial-mesenchymal transition (EMT), Chitosan micelles, Small interfering RNA (siRNA)

Xuan Liu, Xue-Qing Zhou, Xu-Wei Shang, Li Wang, Yi Li, Hong Yuan, Fu-Qiang Hu. Inhibition of chemotherapy-related breast tumor EMT by application of redox-sensitive siRNA delivery system CSO-ss-SA/siRNA along with doxorubicin treatment[J]. Journal of Zhejiang University Science B, 2020, 21(3): 218-233.

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author="Xuan Liu, Xue-Qing Zhou, Xu-Wei Shang, Li Wang, Yi Li, Hong Yuan, Fu-Qiang Hu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

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%T Inhibition of chemotherapy-related breast tumor EMT by application of redox-sensitive siRNA delivery system CSO-ss-SA/siRNA along with doxorubicin treatment
%A Xuan Liu
%A Xue-Qing Zhou
%A Xu-Wei Shang
%A Li Wang
%A Yi Li
%A Hong Yuan
%A Fu-Qiang Hu
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 3
%P 218-233
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900468

T1 - Inhibition of chemotherapy-related breast tumor EMT by application of redox-sensitive siRNA delivery system CSO-ss-SA/siRNA along with doxorubicin treatment
A1 - Xuan Liu
A1 - Xue-Qing Zhou
A1 - Xu-Wei Shang
A1 - Li Wang
A1 - Yi Li
A1 - Hong Yuan
A1 - Fu-Qiang Hu
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 3
SP - 218
EP - 233
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1900468

Metastasis is one of the main reasons causing death in cancer patients. It was reported that chemotherapy might induce metastasis. In order to uncover the mechanism of chemotherapy-induced metastasis and find solutions to inhibit treatment-induced metastasis, the relationship between epithelial-mesenchymal transition (EMT) and doxorubicin (DOX) treatment was investigated and a redox-sensitive small interfering RNA (siRNA) delivery system was designed. DOX-related reactive oxygen species (ROS) were found to be responsible for the invasiveness of tumor cells in vitro, causing enhanced EMT and cytoskeleton reconstruction regulated by ras-related C3 botulinum toxin substrate 1 (RAC1). In order to decrease RAC1, a redox-sensitive glycolipid drug delivery system (chitosan-ss-stearylamine conjugate (CSO-ss-SA)) was designed to carry siRNA, forming a gene delivery system (CSO-ss-SA/siRNA) downregulating RAC1. CSO-ss-SA/siRNA exhibited an enhanced redox sensitivity compared to nonresponsive complexes in 10 mmol/L glutathione (GSH) and showed a significant safety. CSO-ss-SA/siRNA could effectively transmit siRNA into tumor cells, reducing the expression of RAC1 protein by 38.2% and decreasing the number of tumor-induced invasion cells by 42.5%. When combined with DOX, CSO-ss-SA/siRNA remarkably inhibited the chemotherapy-induced EMT in vivo and enhanced therapeutic efficiency. The present study indicates that RAC1 protein is a key regulator of chemotherapy-induced EMT and CSO-ss-SA/siRNA silencing RAC1 could efficiently decrease the tumor metastasis risk after chemotherapy.




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