title: Anti-tumor effect of polysaccharides from Scutellaria barbata D. Don on the 95-D xenograft model via inhibition of the C-met pathway.
abstract: Polysaccharides isolated from Scutellaria barbata (PSB) have been reported to have anti-tumor effects. To investigate the underlying mechanism, a highly invasive, metastatic and phospho-c-Met overexpression lung carcinoma cell, 95-D cell line was used. The results showed that in vitro, PSB not only could inhibit the proliferation of 95-D cell line (IC(50) = 35.2 μg/mL), but also down-regulated the expression of phospho-c-Met and its downstream signaling molecules including phospho-Erk and phospho-Akt. In vivo, PSB inhibited tumor growth in the 95-D subcutaneous xenograft model in a dose-dependent manner; after once-daily intraperitoneal injection for 3 weeks, tumor growth inhibition T/C ratio for 100 and 200 mg/kg treatments was 42.72% and 13.6%, respectively. In the end of the in vivo study, tumor tissues were harvested for further evaluation of the phosphorylation level of c-Met, AKT, and ERK. Ex vivo results demonstrated that the phosphorylation of c-Met and its downstream signaling molecules were also significantly inhibited by PSB. Immunohistochemistry analysis showed dose-dependent inhibition of tumor cell proliferation (Ki67) and reduction of microvessel density (CD31). In summary, the results indicated that PSB exerted anti-tumor growth activity on human lung cancer 95-D in vitro and in vivo by directly regulating the c-Met signaling pathway and the anti-tumor effects were mainly based on its anti-proliferation and anti-angiogenesis action.
authors.affiliation: Department of Dermatology, Daping Hospital, Third Military Medical University, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Yang
authors.forename: Yadong
authors.initials: Y
authors.lastname: Yang
authors.forename: Shuqian
authors.initials: S
authors.lastname: Tang
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.forename: Guihong
authors.initials: G
authors.lastname: Yang
authors.forename: Qiaoyu
authors.initials: Q
authors.lastname: Xu
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use*; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051058:Oncogene Protein v-akt / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry*; D011134:Polysaccharides / Q000494:pharmacology* / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D031363:Scutellaria; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011134:Polysaccharides; C524947:Scutellaria barbata extract; D019859:Proto-Oncogene Proteins c-met; D051058:Oncogene Protein v-akt