Xiao Xing, Chen Wei, Wei Zhe-Wei, Chu Wei-Wei, Lu Xiao-Fang, Li Bo, Chen Hong, Meng Si-Jun, Hao Teng-Fei, Wei Ji-Tao, He Yu-Long, Zhang Chang-Hua
Center of Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People's Republic of China.
Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People's Republic of China.
Onco Targets Ther. 2020 Jun 24;13:6017-6025. doi: 10.2147/OTT.S237431. eCollection 2020.
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.
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.
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.
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.
纳米白蛋白结合型紫杉醇因其低毒性和高效性已被广泛用于治疗乳腺癌和胰腺癌患者。然而,其在胃癌(GC)中的作用仍不明确。我们研究的目的是使用源自GC患者的类器官来测试纳米白蛋白结合型紫杉醇的抗肿瘤活性。
通过使用类器官培养系统,我们描述了从三名胃癌患者的手术样本中建立人胃癌类器官系的过程。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)染色测试癌类器官的特征。通过CCK8测定和Annexin V-FITC/PI染色,使用类器官比较纳米白蛋白结合型紫杉醇、5-氟尿嘧啶和表柔比星的抗肿瘤效率。
成功建立并传代了三个类器官。所建立的GC类器官的形态与原始癌组织一致。纳米白蛋白结合型紫杉醇在hGCO1中的IC50为3.68μmol/L,在hGCO2中为2.41μmol/L,在hGCO3中为2.91μmol/L,显著低于5-氟尿嘧啶(hGCO1中为72.99μmol/L,hGCO2中为28.32μmol/L,hGCO3中为2.91μmol/L)和表柔比星(hGCO1中为25.85μmol/L,hGCO2中为15.15μmol/L,hGCO3中为7.60μmol/L)。当用纳米白蛋白结合型紫杉醇处理每个类器官系的时间增加时,每个类器官中凋亡细胞的百分比相应增加。
纳米白蛋白结合型紫杉醇显示出强大的抗肿瘤活性,有潜力成为治疗GC患者的一线药物。胃癌类器官可能是预测体内药物反应的良好工具。