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Mass Spectrometry Quantification of Anticancer Drug Uptake in Single Multicellular Tumor Spheroids
Zongkai Peng1, Yunpeng Lan1, Susan L Nimmo2
1Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.
Abstract:
Although most advanced-stage ovarian cancers initially respond to platinum- and taxane-based chemotherapy, the majority of them will recur and eventually develop chemoresistance. Among all drug resistance mechanisms, reduced drug uptake in tumors is regarded as an important pathway acquired by drug-resistant cancer cells. For patients with ovarian cancer, chemoresistant cells can develop into multicellular spheroids and spread through ascite fluid that accumulates in their abdomen. These spheroids consist of 3D structures that are highly heterogeneous with different shapes, sizes, and compositions of cell types. Thus, studying drug uptake at the single spheroid level is important for understanding chemosensitivity and chemoresistance; however, drug-uptake studies in single spheroids have not been previously reported due to the lack of a suitable analytical technique. In this study, we cultured spheroids using the ovarian cancer cell line (OVCAR-8) and treated them using paclitaxel or OSW-1, a natural compound with anticancer properties. We then developed a method of quantifying drug uptake in single spheroids using LC/MS measurements and then normalized the drug amount in each spheroid to its size and total protein content. Our method can be used in translational studies of drug development, treatment, and prediction of drug efficacy prior to chemotherapy.
Insights
Researchers developed a new method to measure how much chemotherapy drugs enter individual ovarian cancer spheroids. This technique helps understand drug resistance and predict treatment effectiveness for ovarian cancer patients.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Advanced-stage ovarian cancer often recurs due to chemoresistance, with reduced drug uptake being a key mechanism.
- Chemoresistant ovarian cancer cells form heterogeneous multicellular spheroids in ascites fluid, complicating drug efficacy studies.
- Studying drug uptake at the single spheroid level is crucial for understanding chemoresistance but lacks suitable analytical methods.
Purpose of the Study:
- To develop and validate a novel method for quantifying drug uptake in single ovarian cancer spheroids.
- To assess the utility of this method in understanding drug resistance mechanisms in ovarian cancer.
- To provide a tool for translational studies in drug development and treatment prediction.
Main Methods:
- Cultured ovarian cancer cell line (OVCAR-8) spheroids.
- Treated spheroids with paclitaxel or OSW-1 (a natural anticancer compound).
- Quantified drug uptake in single spheroids using liquid chromatography-mass spectrometry (LC/MS) and normalized to spheroid size and protein content.
Main Results:
- Successfully developed a quantitative method for measuring drug uptake in individual spheroids.
- Demonstrated the ability to measure paclitaxel and OSW-1 uptake in OVCAR-8 spheroids.
- Established a normalization strategy based on spheroid size and total protein content for accurate drug uptake assessment.
Conclusions:
- The developed LC/MS-based method enables precise quantification of drug uptake in single ovarian cancer spheroids.
- This technique offers a valuable tool for investigating drug resistance mechanisms and evaluating drug efficacy in 3D ovarian cancer models.
- The method has potential applications in translational research for drug development and personalized treatment strategies in ovarian cancer.
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