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Isolation and Characterization of Patient-derived Pancreatic Ductal Adenocarcinoma Organoid Models
Published on: January 14, 2020
The Anti-Tumor Effect of Nab-Paclitaxel Proven by Patient-Derived Organoids
Xing Xiao1,2, Wei Chen3, Zhe-Wei Wei4
1Center of Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, People's Republic of China.
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.
Insights
Nab-paclitaxel demonstrates significant anti-tumor activity in gastric cancer (GC) organoids, outperforming traditional chemotherapy drugs. This suggests nab-paclitaxel
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- Nab-paclitaxel is a widely used chemotherapy agent with known efficacy in breast and pancreatic cancers.
- Its therapeutic role in gastric cancer (GC) remains unclear.
- Patient-derived organoids offer a promising model for studying GC and drug responses.
Purpose of the Study:
- To evaluate the anti-tumor activity of nab-paclitaxel in gastric cancer.
- To compare nab-paclitaxel's efficacy against standard chemotherapies (5-FU, epirubicin) in GC.
- To assess the utility of gastric cancer organoids in predicting drug response.
Main Methods:
- Established and characterized human gastric cancer organoid lines from patient samples.
- Validated organoid consistency with original tumor tissues via histopathology.
- Assessed anti-tumor efficacy using CCK8 assays and Annexin V-FITC/PI staining to measure cell viability and apoptosis.
Main Results:
- Successfully established three gastric cancer organoid lines (hGCO1, hGCO2, hGCO3).
- Nab-paclitaxel exhibited significantly lower IC50 values compared to 5-FU and epirubicin across all organoid lines.
- Treatment with nab-paclitaxel led to a dose-dependent increase in apoptotic cells.
Conclusions:
- Nab-paclitaxel displays potent anti-tumor activity in gastric cancer models.
- Nab-paclitaxel holds potential as a first-line treatment for gastric cancer.
- Gastric cancer organoids serve as a valuable tool for predicting patient response to chemotherapy.
