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SKLB-M8 induces apoptosis through the AKT/mTOR signaling pathway in melanoma models and inhibits angiogenesis with decrease of ERK1/2 phosphorylation
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نویسنده
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wang j. ,yang z. ,wen j. ,ma f. ,wang f. ,yu k. ,tang m. ,wu w. ,dong y. ,cheng x. ,nie c. ,chen l.
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منبع
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journal of pharmacological sciences - 2014 - دوره : 126 - شماره : 3 - صفحه:198 -207
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چکیده
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Sklb-m8,a derivative of millepachine,showed significant anti-proliferative effects in melanoma cell lines. in this study,we investigated the anti-melanoma and anti-angiogenic activity of sklb-m8 on three melanoma cell lines (a2058,chl-1,and b16f10) and human umbilical vein endothelial cells (huvecs). in vitro,sklb-m8 showed anti-proliferative activity with ic50 values of 0.07,0.25,and 0.88 μm in a2058,chl-1,and b16f10 cell lines,respectively. flow cytometory analysis showed that sklb-m8 induced g2/m arrest in three melanoma cell lines,and western blotting demonstrated that sklb-m8 down-regulated the expression of cdc2,up-regulated p53 in a2058 and chl-1 cells,and triggered cell apoptosis through down-regulating akt and phosphorylated mtor (p-mtor). sklb-m8 also inhibited huvec proliferation,migration,invasion,and tube formation in vitro with the inhibition of phosphorylated erk1/2 (p-erk1/2). in vivo,alginate-encapsulated tumor cell assay revealed that sklb-m8 suppressed b16f10 tumor angiogenesis. in chl-1- and b16f10-tumor-bearing mouse models,sklb-m8 inhibited tumor growth by oral treatment with less toxicity. cd31 immunofluoresence staining and caspase-3 immunohistochemistry indicated that sklb-m8 inhibited melanoma tumor growth by targeting angiogenesis and inducing caspase3-dependent apoptosis. sklb-m8 might be a potential anti-melanoma drug candidate. © the japanese pharmacological society.
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کلیدواژه
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AKT; Anti-angiogenesis; ERK; Melanoma; P53
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آدرس
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state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041,china,college of chemistry,sichuan university,chengdu,610064, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China, institute of blood transfusion,chinese academy of medical sciences and peking union medical college,chengdu,610081, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China, state key laboratory of biotherapy,west china hospital,sichuan university,chengdu,610041, China
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Authors
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