The Anti-Tumor Effect of Nab-Paclitaxel Proven by Patient-Derived Organoids
The Anti-Tumor Effect of Nab-Paclitaxel Proven by Patient-Derived Organoids
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患者来源的类器官证实白蛋白结合型紫杉醇的抗肿瘤作用
DOI：
10.2147/ott.s237431
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Zhang，Chang-Hua
中科院分区：
文献类型：
--
作者：
Xiao，Xing;Chen，Wei;Zhang，Chang-Hua
研究背景白蛋白结合型紫杉醇（Nab-paclitaxel，Nab-paclitaxel）因其低毒、高效而广泛应用于乳腺癌和胰腺癌的治疗。然而，它在胃癌（GC）中的作用仍然不明确。我们研究的目的是使用GC患者来源的类器官测试nab-紫杉醇的抗肿瘤活性。方法应用类器官培养系统，从3例胃癌手术标本中建立人胃癌类器官系。通过组织病理学检查评估这些类器官与原始癌组织的一致性。使用免疫荧光（IF）染色测试癌症类器官的特征。采用CCK 8法和Annexin V-FITC/PI染色法比较nab-紫杉醇、5-Fu和表阿霉素对类器官的抗肿瘤作用。结果成功建立并传代了3个类器官。建立的GC类器官的形态与原始癌组织一致。白蛋白结合型紫杉醇对hGCO_1、hGCO_2和hGCO_3的IC_（50）分别为3.68 μmol/L、2.41 μmol/L和2.91 μmol/L，明显低于5-FU（hGCO 1、hGCO 2和hGCO 3中分别为72.99 μmol/L、28.32 μmol/L和2.91 μmol/L）和表阿霉素（hGCO 1、hGCO 2和hGCO 3中分别为25.85μ mol/L、15.15 μmol/L和7.60 μmol/L）。当用白蛋白结合型紫杉醇处理每个类器官系增加的时间段时，每个类器官中凋亡细胞的百分比相应地增加。结论白蛋白结合型紫杉醇具有较强的抗肿瘤活性，有望成为治疗胃癌的一线药物。胃癌类器官可能是一个很好的工具，预测在体内对药物的反应。
Background Nab-paclitaxel has been widely used in treating breast cancer and pancreatic patients for its low toxicity and high efficiency. However, its role in gastric cancer (GC) remains ambiguous. The aim of our study was to test the anti-tumor activity of nab-paclitaxel using GC patient-derived organoids. Methods By using the organoid culture system, we describe the establishment of human gastric cancer organoid lines from surgical samples of three patients with gastric cancer. The consistency of these organoids with original cancer tissues was evaluated by histopathological examination. The characteristics of the cancer organoids were tested using immunofluorescence (IF) staining. Using organoids, the anti-tumor efficiencies of nab-paclitaxel, 5-Fu and epirubicin were compared by CCK8 assay and Annexin V-FITC/PI staining. Results Three organoids were successfully established and passaged. The morphology of the established GC organoids was consistent with original cancer tissues. The IC50 of nab-paclitaxel was 3.68 μmol/L in hGCO1, 2.41 μmol/L in hGCO2 and 2.91 μmol/L in hGCO3, which was significantly lower than those of 5-FU (72.99 μmol/L in hGCO1, 28.32 μmol/L in hGCO2 and 2.91 μmol/L in hGCO3) and epirubicin (25.85μmol/L in hGCO1, 15.15 μmol/L in hGCO2 and 7.60 μmol/L in hGCO3). When each organoid lines were treated with nab-paclitaxel for increasing period of time, the percentage of the apoptotic cells in each organoid increased accordingly. Conclusion Nab-paclitaxel showed strong anti-tumor activity and had the potential to become front-line drug for treating GC patients. Gastric cancer organoid may be a good tool to predict in vivo response to drugs.