| Summary: | 碩士 === 國立中興大學 === 醫學科技研究所 === 97 === Background and Aims: Honokiol, a small molecular natural product, has been shown to possess potent anti-neoplastic and anti-angiogenic properties. However, the molecular mechanism underlying the anticancer activity is poorly understood. We examined the in vitro and in vivo effects of PPAR-gamma and c-Met on cell growth, angiogenesis of gastric cancer and the cancer regulated genes-C/EBP beta. Methods: Four gastric cancer cell lines were used. Immunohistochemistry and immunoblotting were used to assess PPAR-gamma and c-Met expression levels in xenograft gastric cancer tumour model and cancer cell lines, respectively. MTT assay, flow cytometry and soft agar assay were used to examine tumour growth. HUVECs tube formation, rat aorta ring assay were employed to assess anti-angiogenic effect. Gelatin zymography, transwell chamber were utilized to investigates invasion and migration. Tumour growth and metastasis were analyzed in mice injected with pure compound Honokiol administered. Moreover, identification of C/EBP beta phosphorylation and translocation were analyzed by immunoprecipitation, nuclear/cytosol protein extraction and immunofluorescence staining assay. Results: PPAR-gamma, c-Met and C/EBP beta overexpression were found in gastric cancer model in vitro and in vivo. Honokiol significantly inhibited tumour growth, migration, invasion and tube formation. In xenograft gastric cancer model,we found Honokiol completely abolished peritoneal metastasis and angiogenesis better than subcutaneous suppressed tumor burden. Activation of calpain II , dephosphorylation and translocation change of C/EBP beta by Honokoil were able to down regulate PPAR-gamma, c-Met and C/EBP beta expression. Conclusions: A novel molecular Honokiol, inhibits tumor growth and angiogenesis, may be a promising drug candidate in anti-angiogenesis and anticancer agent.
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