Mass Spectrometry Quantification of Anticancer Drug Uptake in Single Multicellular Tumor Spheroids.

Autor:	Peng Z; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States., Lan Y; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States., Nimmo SL; Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73117, United States., Bui RH; Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73117, United States.; Department of Obstetrics & Gynecology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States., Benbrook DM; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States.; Department of Obstetrics & Gynecology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States.; Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73117, United States., Burgett AWG; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States.; Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73117, United States., Yang Z; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States.
Jazyk:	angličtina
Zdroj:	ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2024 Sep 30; Vol. 7 (10), pp. 3011-3016. Date of Electronic Publication: 2024 Sep 30 (Print Publication: 2024).
DOI:	10.1021/acsptsci.4c00525
Abstrakt:	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. Competing Interests: The authors declare no competing financial interest. (© 2024 American Chemical Society.)
Databáze:	MEDLINE
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