Effect of Noscapine and its derivative, EM101, on renal cell cancer and their mechanisms

Noscapine及其衍生物EM101抗肾细胞癌的作用及其机制

• 批准号: 23592327
• 负责人: MIYAGI Toru
• 金额: $ 3.41万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592327/
• 关键词: Noscapine; renal cell cancer; prostate cancer; flavonoids; docetaxel; ノスカピン; 前立腺癌; パクリタキセル耐性; 植物フラボノイド; ドセタキセル耐性; 腎癌

Noscapine is clinically available safe medicine, and antitumor action is found in MDR-overexpressing cancer. Because it was considered that MDR overexpression was involved in drug resistance of the renal carcinoma, we added Noscapine to renal carcinoma cells ACHN and confirmed antitumor effect in in vitro and in vivo. We confirmed antitumor effect in the prostate cancer cell line. Noscapine inhibited the proliferation of not only androgen-independent prostate caner cells DU145 but also DU145-TxR which is resistant for paclitaxel and docetaxel.DU145-TxR overexpressed MDR mRNA and p-glycoprotein that stimulate.For the purpose of expecting a synergistic effect with noscapine and flavonoids in prostate cancer, we investigated the effect of flavonoids on the androgen responsiveness. After LNCaP cells were transfected with PSA promoter-driven Luciferase reporter, cells were treated with DHT with flavonoids. Then naringenin showed the strong suppression of androgen responsiveness.

那斯卡品是临床上可用的安全药物，在 MDR 过度表达的癌症中发现了抗肿瘤作用。由于认为MDR过表达与肾癌耐药有关，因此我们将Noscapine添加到肾癌细胞ACHN中，并在体外和体内证实了抗肿瘤作用。我们证实了对前列腺癌细胞系的抗肿瘤作用。 Noscapine不仅抑制雄激素非依赖性前列腺癌细胞DU145的增殖，还抑制对紫杉醇和多西他赛耐药的DU145-TxR的增殖。DU145-TxR过表达MDR mRNA和刺激的p-糖蛋白。以期与Noscapine产生协同作用和黄酮类化合物在前列腺癌中的作用，我们研究了黄酮类化合物对雄激素反应性的影响。 LNCaP 细胞用 PSA 启动子驱动的荧光素酶报告基因转染后，用含有类黄酮的 DHT 处理细胞。然后柚皮素表现出强烈的雄激素反应性抑制作用。