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128th General Meeting of Korean Chemical Society Investigation of TPT-VCR multidrug mechanisms in 3D spheroids human neuroblastoma cells

Submission Date :
8 / 19 / 2021 , 15 : 01 : 04
Abstract Number :
128081946297
Presenting Type:
Oral Presentation
Presenting Area :
Analytical Chemistry - Oral Presentation of Young Analytical Chemists II
Authors :
Sooyeon Chae, Chae Ri Park, MyungKook Son, Dongjoon Im, Hugh I. Kim*
Department of Chemistry, Korea University, Korea
Assigned Code :
ANAL2.O-3 Assigend Code Guideline
Presenting Time :
FRI, 09 : 12
Neuroblastoma is a common extracranial solid tumor in childhood, which begins when immature nerve cells grow out of control in the adrenal gland, abdomen, pelvis, chest, and neck. Multidrug regimen chemotherapy has been underway to optimize therapeutic outcomes, maximize treatment efficiency. The multidrug regimen with topotecan and vincristine was used for neuroblastoma patients. Topotecan (TPT) is an anti-tumor drug that forms a ternary complex into [topoisomerase I-DNA-TPT], preventing DNA replication. Vincristine (VCR) is also an anti-tumor drug, and its mechanism of action is interaction with tubulin to inhibit mitosis. Several clinical tests showed that the multidrug regimen with TPT and VCR have synergistic toxicity. However, the specific mechanism of this effect is still ambiguous due to challenges at mimicry of pharmacokinetics and the tumor microenvironment at the laboratory level. In this study, we aim to investigate TPT-VCR multidrug mechanisms and mimic pharmacokinetics and tumor microenvironment. 3D spheroid SK-N-SH neuroblastoma cells treated with TPT and VCR multidrug showed a synergistic effect compare to single-drug treatment. The tubulin polymerization data showed that the action of vincristine was reduced in multidrug treatment, which implies another pathway for a synergistic effect. For more detailed investigation, we plan to mimic pharmacokinetics and tumor microenvironment using A fluidic system.