Abstract
In the present study, we have undertaken pharmacodynamic studies of HM-3 in vitro and in vivo. A dual function of HM-3 with various doses was observed. HM-3 at low dose revealed obvious anticancer activity. In contrast, HM-3 at high dose had a tendency to promote tumorigenesis and tumor metastasis. Microarray analysis demonstrated that HM-3 at high dose could up-regulate the transcription of AKT1 and MEK1, which resulted in the promotion of tumorigenesis and metastasis. Therefore, the dose of angiogenesis inhibitors plays a critical role in cancer treatment. In order to achieve the ideal effect of angiogenesis inhibitor drugs on cancer treatment, a ful exploration of administration dose, frequency, and period for this kind of drugs is highly desired.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / administration & dosage
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Angiogenesis Inhibitors / chemistry*
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Angiogenesis Inhibitors / pharmacology
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Angiogenesis Inhibitors / therapeutic use*
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Animals
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Cell Line
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Cell Movement / drug effects
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Nude
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 3 / genetics
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Neoplasms / blood supply*
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Neoplasms / drug therapy*
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Neoplasms / pathology
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Oligopeptides / administration & dosage
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Oligopeptides / chemistry*
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Oligopeptides / pharmacology
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Oligopeptides / therapeutic use*
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Organ Culture Techniques
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Peptides / administration & dosage
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Peptides / chemistry
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Peptides / pharmacology
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Peptides / therapeutic use
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Proto-Oncogene Proteins c-akt / genetics
Substances
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Angiogenesis Inhibitors
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Oligopeptides
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Peptides
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arginyl-glycyl-aspartic acid
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3