科学家发现逆转三阴性乳腺癌对化疗耐药的新方法

　　由于三阴性乳腺癌缺乏靶向疗法，故其全身治疗主要依靠化疗，而化疗耐药性是三阴性乳腺癌治疗的主要障碍。

　　2017年11月21日，英国《自然》旗下《科学报告》在线发表美国佛罗里达农工大学、迈阿密大学、圣约翰大学的研究报告，发现通过诺斯卡品的化疗增敏作用，可以逆转三阴性乳腺癌对多西他赛的耐药性。

诺斯卡品：又称那可丁，为苄基异喹啉生物碱，来自罂粟科植物，无止痛作用，主要用于止咳。此类生物碱还包括小檗胺、千金藤素、轮环藤宁、箭毒碱、左旋箭毒碱、紫唐松草碱、去氢大叶唐松草任、高原唐松草亭、大叶唐松草任、唐松草亭、唐松草西宾、防己诺林碱、粉防己碱或汉防己碱、汉防己甲素、汉防己乙素、莲心碱、甲基莲心碱、异莲心碱、蝙蝠葛碱、蝙蝠葛苏林碱等，均有不同抗癌作用。

　　该研究首次调查了低浓度诺斯卡品＋多西他赛克服三阴性乳腺癌耐药性的化学增敏作用。

　　体外研究表明，诺斯卡品可以显著抑制野生型（P<0.01）和耐药型（P<0.05）三阴性乳腺癌细胞的增殖。三维立体细胞培养模型与传统二维平面细胞培养系统相比，诺斯卡品→多西他赛治疗可以显著抑制细胞生存能力（～1.3倍，P<0.05）。

　　体内研究表明，口服诺斯卡品100mg/kg然后静脉注射脂质体多西他赛5mg/kg，野生型和耐药型异种移植肿瘤均显著缩小。

　　对于野生型，诺斯卡品＋多西他赛

• 与诺斯卡品相比：肿瘤体积减少5.49倍 （P<0.001）

• 与多西他赛相比：肿瘤体积减少3.25倍 （P<0.001）

　　对于耐药型，诺斯卡品＋多西他赛

• 与诺斯卡品相比：肿瘤体积减少2.33倍 （P<0.05）

• 与多西他赛相比：肿瘤体积减少1.41倍 （P<0.05）

• 并且减少了抗凋亡因子和多药耐药性蛋白质的表达

　　因此，诺斯卡品→多西他赛方案的化疗增敏作用，提供了令人鼓舞的化疗策略，对耐药型三阴性乳腺癌的治疗具有重大意义。

Sci Rep. 2017 Nov 20;7(1):15824.

Reversal of drug-resistance by noscapine chemo-sensitization in docetaxel resistant triple negative breast cancer.

Ravi Doddapaneni, Ketan Patel, Nusrat Chowdhury, Mandip Singh.

Florida A&M University, Tallahassee, FL, USA; University of Miami, Miami, FL, USA; St. John's University, Queens, NY, USA.

Multidrug resistance (MDR) is a major impediment to cancer treatment. Here, for the first time, we investigated the chemo-sensitizing effect of Noscapine (Nos) at low concentrations in conjunction with docetaxel (DTX) to overcome drug resistance of triple negative breast cancer (TNBC). In vitro experiments showed that Nos significantly inhibited proliferation of TNBC wild type (p<0.01) and drug resistant (p<0.05) TNBC cells. Nos followed by DTX treatment notably increased the cell viability (~1.3 fold) markedly (p<0.05) in 3D models compared to conventional 2D systems. In vivo oral administration of Nos (100mg/kg) followed by intravenous DTX (5mg/kg) liposome treatment revealed regression of xenograft tumors in both wild type (p<0.001) and drug-resistant (p<0.05) xenografts. In wild type xenografts, combination of Nos plus DTX group showed 5.49 and 3.25 fold reduction in tumor volume compared to Nos and DTX alone groups, respectively. In drug-resistant xenografts, tumor volume was decreased 2.33 and 1.41 fold in xenografts treated with Nos plus DTX significantly (p<0.05) compared to Nos and DTX alone respectively and downregulated the expression of anti-apoptotic factors and multidrug resistance proteins. Collectively, chemo-sensitizing effect of Nos followed by DTX regime provide a promising chemotherapeutic strategy and its significant role for the treatment of drug-resistant TNBC.

DOI: 10.1038/s41598-017-15531-1