CLC number: R945
On-line Access: 2020-03-05
Received: 2019-08-02
Revision Accepted: 2019-10-24
Crosschecked: 2020-02-22
Cited: 0
Clicked: 3744
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.
@article{title="Inhibition of chemotherapy-related breast tumor EMT by application of redox-sensitive siRNA delivery system CSO-ss-SA/siRNA along with doxorubicin treatment",
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",
volume="21",
number="3",
pages="218-233",
year="2020",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900468"
}
%0 Journal Article
%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
TY - JOUR
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
ER -
DOI - 10.1631/jzus.B1900468
Abstract: 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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