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.

诺斯卡品是临床上可获得的安全药物，并且在MDR过度表达的癌症中发现抗肿瘤作用。由于MDR过度表达被认为与肾癌耐药有关，我们将诺斯卡品加入肾癌细胞ACHN中，并在体外和体内证实其抗肿瘤作用。我们在前列腺癌细胞系中证实了抗肿瘤作用。Noscapine不仅能抑制雄激素非依赖性前列腺癌细胞DU 145的增殖，还能抑制对紫杉醇和紫杉醇耐药的DU 145-TxR细胞的增殖，DU 145-TxR细胞能过表达MDR mRNA和P-糖蛋白，从而促进细胞的增殖。在用PSA启动子驱动的荧光素酶报告基因转染LNCaP细胞后，用具有类黄酮的DHT处理细胞。结果表明，柚皮素对雄激素反应性有较强的抑制作用。