Liposomal Curcumin Targeting Endometrial Cancer Through the NF-κB Pathway

被引:40
|
作者
Xu, Hanzi [1 ,2 ]
Gong, Zhen [3 ]
Zhou, Siying [1 ]
Yang, Sujin [4 ]
Wang, Dandan [4 ]
Chen, Xiu [4 ]
Wu, Jiaqi [5 ]
Liu, Liucheng [6 ]
Zhong, Shanliang [2 ]
Zhao, Jianhua [2 ]
Tang, Jinhai [1 ,4 ]
机构
[1] Nanjing Univ Chinese Med, Sch Clin Med 1, Nanjing 210023, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Affiliated Canc Hosp, Jiangsu Canc Hosp, Jiangsu Inst Canc Res, Nanjing, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Nanjing Matern & Child Hlth Care Hosp, Dept Gynecol, Affiliated Obstet & Gynecol Hosp, Nanjing, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Affiliated Hosp 1, Dept Gen Surg, Nanjing, Jiangsu, Peoples R China
[5] Nanjing Tech Univ, Coll Biotechnol & Pharmaceut Engn, Inst Translat Med, Nanjing, Jiangsu, Peoples R China
[6] Jiangsu Aosakang Pharmaceut Co Ltd, Dept Pharm, Nanjing, Jiangsu, Peoples R China
关键词
Endometrial carcinoma; Liposomal curcumin; NF-kappa B; ANTICANCER ACTIVITY; BREAST-CANCER; TUMOR-GROWTH; INHIBITION; CARCINOMA; DELIVERY; CELLS; ACID;
D O I
10.1159/000491886
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background/Aims: Emerging evidence suggests that curcumin possesses chemopreventive properties against various cancers. However, its poor bioavailability limits its clinical application. In this study, we aimed to utilize encapsulation in liposomes (Lipo) as a strategy for the clinical administration of curcumin for endometrial carcinoma (EC). Methods: Curcumin was encapsulated in a liposomal delivery system to prepare a formulation of liposomal curcumin (LC). EC cell lines Ishikawa and HEC-1 were treated with the compound and cell proliferation was measured using MTT assay. Hoechst 33258 staining assay and flow cytometry were used to detect apoptosis of the cells. Wound healing and cell invasion assays were employed to monitor cell motility. Underlying target signaling, such as NF-kappa B, caspases, and MMPs, were further studied via qRT-PCR and western blot. Thereafter, a zebrafish model was used to assess the toxicity of LC. Finally, a zebrafish transplantation tumor model of EC was grown and treated with LC. Tumors were monitored and harvested to study the expression of NF-kappa B. Results: The formation of LC was successfully developed with excellent purity and physical properties. In vitro, LC resulted in dose-dependent inhibition of proliferation, induction of apoptosis, and suppression of Ishikawa and HEC-1 cell motility. LC treatment also suppressed the activation and/or expression of NF-kappa B, caspase-3, and MMP-9. No demonstrable toxicity was found in the zebrafish model and tumors were suppressed after treatment with LC. PCR analysis also showed down-regulated expression of NF-kappa B. Conclusions: LC was successfully prepared and played biological roles against EC probably through negative regulation of the NF-kappa B pathway in vitro and in vivo, which demonstrates its potential therapeutic effects in EC. (c) 2018 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:569 / 582
页数:14
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