OncoTargets and Therapy (Jun 2020)
The Anti-Tumor Effect of Nab-Paclitaxel Proven by Patient-Derived Organoids
Abstract
Xing Xiao,1,2,* Wei Chen,3,* Zhe-Wei Wei,4,* Wei-Wei Chu,2 Xiao-Fang Lu,3 Bo Li,1,2 Hong Chen,1 Si-Jun Meng,1 Teng-Fei Hao,1 Ji-Tao Wei,1,2 Yu-Long He,1 Chang-Hua Zhang1 1Center of Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 2Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 3Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 4Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-Hua Zhang; Yu-Long He Email [email protected]; [email protected]: 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.Keywords: nab-paclitaxel, organoid, gastric cancer, anti-tumor
