Zheng Zeng1, Caiji Lin2, Siwen Wang2, Pengfei Wang2, Wenwen Xu2, Wenqing Ma2, Jiali Wang2, Qian Xiang2, Yiting Liu2, Jiaming Yang2, Fan Ye2, Kaihong Xie2, Jian Xu2, Yao Luo2, Shu-Lin Liu3, Huidi Liu4. 1. Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, No. 157, Baojian Road, Harbin, China; HMU-UCCSM Centre for Infection and Genomics, Harbin, 150081, China; Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, T2N 4N1, Canada. 2. Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, No. 157, Baojian Road, Harbin, China; HMU-UCCSM Centre for Infection and Genomics, Harbin, 150081, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Heilongjiang, China. 3. Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, No. 157, Baojian Road, Harbin, China; HMU-UCCSM Centre for Infection and Genomics, Harbin, 150081, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Heilongjiang, China; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, T2N 4N1, Canada. Electronic address: slliu@hrbmu.edu.cn. 4. Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, No. 157, Baojian Road, Harbin, China; HMU-UCCSM Centre for Infection and Genomics, Harbin, 150081, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Heilongjiang, China; Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, T2N 4N1, Canada. Electronic address: hdliu@hrbmu.edu.cn.
Abstract
BACKGROUND: Epithelial carcinoma is a subtype of ovarian cancers, with the highest lethality among all ovarian cancer subtypes. Hitherto surgical excision combined with chemotherapy has been the most extensively employed method in clinical treatment. However, the disease relapses very frequently, calling for more effective therapies. Mangiferin, a natural xanthone glucoside, has displayed promising anti-cancer activities by in vitro studies, but its therapeutic value in epithelial ovarian cancer treatment, either by in vivo or in vitro studies, remained to be known. PURPOSE: This study aimed to determine the suppressive activities of mangiferin on human epithelial ovarian cancer and elucidate the underlying molecular mechanisms. STUDY DESIGN AND METHODS: We employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the crystal violet assay to determine the half maximal inhibitory concentration (IC50) values of mangiferin with paclitaxel as a positive control and the inhibitory effects of mangiferin on the proliferation of two human epithelial ovarian cancer cell lines. Wound healing and Transwell assays were used to determine anti-metastastic activities of mangiferin. ES-2 xenograft nude mouse model was used for the in vivo experiments. Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assays were carried out for evaluating the expression level of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). RESULTS: In the present study, we demonstrated by both in vitro and in vivo assays that mangiferin suppressed the progress of epithelial ovarian cancer in a dose-dependent manner. In the animals treated with mangiferin, the tumor volume and weight were reduced significantly. Analyses of involved molecular events demonstrated that mangiferin down-regulated the expression of metastasis-associated proteins MMP2 and MMP9. CONCLUSION: Mangiferin strongly inhibited the progression of human epithelial ovarian cancer by down-regulating MMP2 and MMP9.
BACKGROUND:Epithelial carcinoma is a subtype of ovarian cancers, with the highest lethality among all ovarian cancer subtypes. Hitherto surgical excision combined with chemotherapy has been the most extensively employed method in clinical treatment. However, the disease relapses very frequently, calling for more effective therapies. Mangiferin, a natural xanthone glucoside, has displayed promising anti-cancer activities by in vitro studies, but its therapeutic value in epithelial ovarian cancer treatment, either by in vivo or in vitro studies, remained to be known. PURPOSE: This study aimed to determine the suppressive activities of mangiferin on humanepithelial ovarian cancer and elucidate the underlying molecular mechanisms. STUDY DESIGN AND METHODS: We employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the crystal violet assay to determine the half maximal inhibitory concentration (IC50) values of mangiferin with paclitaxel as a positive control and the inhibitory effects of mangiferin on the proliferation of two humanepithelial ovarian cancer cell lines. Wound healing and Transwell assays were used to determine anti-metastastic activities of mangiferin. ES-2 xenograft nude mouse model was used for the in vivo experiments. Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assays were carried out for evaluating the expression level of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). RESULTS: In the present study, we demonstrated by both in vitro and in vivo assays that mangiferin suppressed the progress of epithelial ovarian cancer in a dose-dependent manner. In the animals treated with mangiferin, the tumor volume and weight were reduced significantly. Analyses of involved molecular events demonstrated that mangiferin down-regulated the expression of metastasis-associated proteins MMP2 and MMP9. CONCLUSION:Mangiferin strongly inhibited the progression of humanepithelial ovarian cancer by down-regulating MMP2 and MMP9.
Authors: Veeranjaneya Reddy Lebaka; Young-Jung Wee; Weibing Ye; Mallikarjuna Korivi Journal: Int J Environ Res Public Health Date: 2021-01-16 Impact factor: 3.390