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J Biomater Sci Polym Ed. 2016;27(7):545-56. doi: 10.1080/09205063.2015.1131667. Epub 2016 Mar 16.

Enhancement of triptolide-loaded micelles on tumorigenicity inhibition of human ovarian cancer.

Wang Y1,2, Liu T1,2, Li H3,2.

Author information

1
b Department of Obstetrics and Gynecology , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200001 , PR China.
2
c Focus Construction Subject of Shanghai Education Department , Shanghai Key Laboratory of Gynecologic Oncology , Shanghai 200127 , China.
3
a Department of Traditional Chinese Medicine , Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200001 , PR China.

Abstract

Triptolide (TP), a diterpenoid obtained from Tripterygium wilfordii Hook.f, has shown its antitumor activities against a variety of cancers in vitro in recent years. Unfortunately, TP has a small margin between the therapeutic and toxic doses and shows serious toxicity which limits its uses in antitumor treatment. In our previous study, Triptolide-loaded micelles (TP micelles), a TP drug delivery system with a sustained release behavior, had been reported to decrease TP uptake in the liver to relieve its toxicity, and increase TP distribution in the ovary to enhance its effects. This work therefore aimed at evaluating the inhibitory ability of TP micelles in the proliferation, apoptosis, invasion, and migration, and compared with free TP in SKOV3 cells. Our results showed that TP micelles inhibited the proliferation of SKOV3 in a time- and dose-dependent manner, and exhibited enhanced inhibition following 48 and 72 h treatment compared to TP. Cell cycle analysis revealed that TP and TP micelles inhibited cell proliferation by blocking their progression from the G2/M phase to the S phase. Although TP induced a significant increase in cell apoptosis, TP micelles showed a superior effect following 48 and 72 h treatment. Induction of caspase-dependent way and inhibition of NF-κB activation were found to be involved in the mechanism of TP micelles-induced apoptosis. Furthermore, the wound healing assay and transwell assay showed that both TP and TP micelles could obviously inhibit SKOV3 cells migration and invasion. Overall, TP micelles exhibited enhanced therapeutic efficacy in ovarian cancer in vitro due to its prolonged release and redistribution compared with the free TP. TP micelles might lead to an increase in tumorigenicity inhibition and a decrease in resistance and incidence simultaneously, indicating that it offers a new strategy with promising characteristics for TP chemotherapy application for ovarian cancer.

KEYWORDS:

Triptolide (TP); Triptolide-loaded micelles (TP micelles); apoptosis; invasion; migration; proliferation

PMID:
26786618
DOI:
10.1080/09205063.2015.1131667
[Indexed for MEDLINE]

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