科學家發現逆轉三陰性乳腺癌對化療耐藥的新方法

2023年12月9日發(作者：樂之培優)

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科學家發現逆轉三陰性乳腺癌對化療耐藥的新方法

由于三陰性乳腺癌缺乏靶向療法，故其全身治療主要依靠化療，而化療耐藥性是三陰性乳腺癌治療的主要障礙。

2017年11月21日，英國《自然》旗下《科學報告》在線發表美國佛羅里達農工大學、邁阿密大學、圣約翰大學的研究報告，發現通過諾斯卡品的化療增敏作用，可以逆轉三陰性乳腺癌對多西他賽的耐藥性。

諾斯卡品：又稱那可丁，為芐基異喹啉生物堿，來自罌粟科植物，無止痛作用，主要用于止咳。此類生物堿還包括小檗胺、千金藤素、輪環藤寧、箭毒堿、左旋箭毒堿、紫唐松草堿、去氫大葉唐松草任、高原唐松草亭、大葉唐松草任、唐松草亭、唐松草西賓、防己諾林堿、粉防己堿或漢防己堿、漢防己甲素、漢防己乙素、蓮心堿、甲基蓮心堿、異蓮心堿、蝙蝠葛堿、蝙蝠葛蘇林堿等，均有不同抗癌作用。

該研究首次調查了低濃度諾斯卡品＋多西他賽克服三陰性乳腺癌耐藥性的化學增敏作用。

體外研究表明，諾斯卡品可以顯著抑制野生型（P<0.01）和耐藥型（P<0.05）三陰性乳腺癌細胞的增殖。三維立體細胞培養模型與傳統二維平面細胞培養系統相比，諾斯卡品→多西他賽治療可以顯著抑制細胞生存能力（～1.3倍，P<0.05）。

體內研究表明，口服諾斯卡品100mg/kg然后靜脈注射脂質體多西他賽5mg/kg，野生型和耐藥型異種移植腫瘤均顯著縮小。

對于野生型，諾斯卡品＋多西他賽

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與諾斯卡品相比：腫瘤體積減少?

與多西他賽相比：腫瘤體積減少5.49倍 （P<0.001）

3.25倍 （P<0.001）

對于耐藥型，諾斯卡品＋多西他賽 ?

與諾斯卡品相比：腫瘤體積減少?

與多西他賽相比：腫瘤體積減少2.33倍 （P<0.05）

1.41倍 （P<0.05）

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并且減少了抗凋亡因子和多藥耐藥性蛋白質的表達

因此，諾斯卡品→多西他賽方案的化療增敏作用，提供了令人鼓舞的化療策略，對耐藥型三陰性乳腺癌的治療具有重大意義。

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

Reversal of drug-resistance by noscapine chemo-nsitization in docetaxel resistant triple negative breast

cancer.

Ravi Doddapaneni, Ketan Patel, Nusrat Chowdhury, Mandip

Singh.

Florida A&M University, Tallaha, 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-nsitizing 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 incread 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 decread 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-nsitizing 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

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