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抑制溶血磷脂酰肌醇转运体ABCC1可降低前列腺癌细胞的生长并增强对化疗的敏感性。

Inhibition of the Lysophosphatidylinositol Transporter ABCC1 Reduces Prostate Cancer Cell Growth and Sensitizes to Chemotherapy.

作者信息

Emmanouilidi Aikaterini, Casari Ilaria, Gokcen Akkaya Begum, Maffucci Tania, Furic Luc, Guffanti Federica, Broggini Massimo, Chen Xi, Maxuitenko Yulia Y, Keeton Adam B, Piazza Gary A, Linton Kenneth J, Falasca Marco

机构信息

Metabolic Signalling Group, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia.

Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.

出版信息

Cancers (Basel). 2020 Jul 23;12(8):2022. doi: 10.3390/cancers12082022.

Abstract

Expression of ATP-binding cassette (ABC) transporters has long been implicated in cancer chemotherapy resistance. Increased expression of the ABCC subfamily transporters has been reported in prostate cancer, especially in androgen-resistant cases. ABCC transporters are known to efflux drugs but, recently, we have demonstrated that they can also have a more direct role in cancer progression. The pharmacological potential of targeting ABCC1, however, remained to be assessed. In this study, we investigated whether the blockade of ABCC1 affects prostate cancer cell proliferation using both in vitro and in vivo models. Our data demonstrate that pharmacological inhibition of ABCC1 reduced prostate cancer cell growth in vitro and potentiated the effects of Docetaxel in vitro and in mouse models of prostate cancer in vivo. Collectively, these data identify ABCC1 as a novel and promising target in prostate cancer therapy.

摘要

长期以来,ATP结合盒(ABC)转运蛋白的表达一直被认为与癌症化疗耐药性有关。据报道,ABCC亚家族转运蛋白在前列腺癌中表达增加,尤其是在雄激素抵抗的病例中。已知ABCC转运蛋白可外排药物,但最近我们发现它们在癌症进展中也可发挥更直接的作用。然而,靶向ABCC1的药理学潜力仍有待评估。在本研究中,我们使用体外和体内模型研究了ABCC1的阻断是否会影响前列腺癌细胞的增殖。我们的数据表明,ABCC1的药理学抑制在体外降低了前列腺癌细胞的生长,并在体外和前列腺癌小鼠体内模型中增强了多西他赛的作用。总体而言,这些数据表明ABCC1是前列腺癌治疗中一个新的且有前景的靶点。

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