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As shown in Figure 6, a single dose of minocycline resulted in significant decrease in tumor HIF-1�� levels after both 4 (65 �� 5%, p selleck compound from single-dose minocycline treated animals after both 4 and 24 h (p MMP23B in female BALB/c athymic nude mice bearing i.p. OVCAR-3 tumors. Whole cell protein lysates of tumor tissues excised from mice subjected ... Discussion HIF-1 is a key cellular survival protein with critical roles in tumor progression, angiogenesis and metastasis [1]. We and others have recently indicated the anti-tumor activities of minocycline [16,35] correlated with its inhibitory effects on angiogenesis [36] and VEGF expression [17]. However, the mechanisms behind these effects is not well-defined. Based on the pivotal role of HIF-1 in tumor angiogenesis and VEGF expression, it is possible that modulation of this transcription factor is one of the key mechanisms Selleck Venetoclax of action of minocycline. The major aim of the current study was to determine the effects of minocycline on HIF-1 in ovarian cancer. In vitro, using ovarian cancer cells, we found that minocycline inhibited the HIF-1�� surge induced by hypoxia or hypoxic mimetic agent DFO. This was followed by acute (4 and 24 hours) treatment of ovarian tumor-bearing mice with minocycline. Analysis of tumors collected from these mice revealed down-regulation of HIF-1�� in minocycline-treated animals. HIF-1�� protein expression is predominantly regulated via its stability regulation [21].