Hanzi Xu1,2, Zhen Gong3, Siying Zhou1, Sujin Yang4, Dandan Wang4, Xiu Chen4, Jiaqi Wu5, Liucheng Liu6, Shanliang Zhong2, Jianhua Zhao2, Jinhai Tang1,4. 1. The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China. 2. Jiangsu Institute of Cancer Research, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China. 3. Department of Gynecology, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China. 4. Department of General Surgery, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China. 5. Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China. 6. Department of Pharmacy, Jiangsu Aosakang Pharmaceutical Co. Ltd., Nanjing, China.
Abstract
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-κB, 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-κB. 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-κB, 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-κB. CONCLUSIONS: LC was successfully prepared and played biological roles against EC probably through negative regulation of the NF-κB pathway in vitro and in vivo, which demonstrates its potential therapeutic effects in EC.
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-κB, 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-κB. 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-κB, 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-κB. CONCLUSIONS:LC was successfully prepared and played biological roles against EC probably through negative regulation of the NF-κB pathway in vitro and in vivo, which demonstrates its potential therapeutic effects in EC.