多巴胺受体与卵巢癌治疗
首发时间:2016-01-15
摘要:多巴胺受体分为D1类(D1、D5)和D2类(D2、D3和D4),卵巢癌细胞中检出除D3外的其余四种受体。多巴胺通过D1受体介导的cAMP-PKA信号通路的作用稳定肿瘤血管从而增加抗肿瘤药物的摄取。同时也通过D2受体介导的Src抑制,降低VEGF和HIF-1α水平,从而抑制慢性应激引起的肿瘤血管生成和利于肿瘤生长的微环境的形成。D2受体拮抗剂通过VEGFR-2/PI3K/mTOR通路促进肿瘤细胞凋亡,进而抑制肿瘤的生长。多巴胺受体可能通过抑制肿瘤血管生成、正常化肿瘤血管功能、减少抗肿瘤药物外排、抑制肿瘤免疫逃避、促进肿瘤细胞凋亡和细胞周期阻滞等发挥其抗肿瘤作用。多巴胺受体可能成为卵巢癌治疗的新靶点。
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Dopamine Receptor and Treatment of Ovarian Cancer
Abstract:Five subtypes of dopamine receptors can be grouped into two classes: the D1-like receptor class (i.e., D1 and D5 ) and D2-like receptor class (i.e., D2, D3 and D4). All dopamine receptors are detected in human ovarian cancer cells except D3. Dopamine favors the uptake of antitumor drugs via vascular stabilization due to the cAMP-PKA signal pathway mediated by DR1, and can reverse angiogenesis and the permissive microenvironment for tumor growth attributable to chronic stress via the D2-mediated Src inhibition and decrease of VEGF and HIF-1α. An antagonist of D2 can enhance apoptosis of cancer cells and inhibit tumor growth by targeting the VEGFR-2/PI3K/mTOR signal pathway. Thus, dopamine receptor can be a target for treatment of ovarian cancer.
Keywords: Dopamine receptor ovarian cance agonist antagonist
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