Non-linear Dose Response of Lymphocyte Cell Lines to Microtubule Inhibitors.

作者: Daria M. Potashnikova , Aleena A. Saidova , Anna V. Tvorogova , Eugene V. Sheval , Ivan A. Vorobjev

DOI: 10.3389/FPHAR.2019.00436

关键词:

摘要: Microtubule (MT) inhibitors show anti-cancer activity in a wide range of tumors vitro and demonstrate high clinical efficacy. To date they are routinely included into many chemotherapeutic regimens. While the mechanisms MT inhibitors’ interactions with tubulin have been well-established, relationship between their concentration effect on neoplastic cells is not completely understood. The common notion that tumor most vulnerable during division all block them mitosis induce mitotic checkpoint-associated cell death. At same time multiple evidence more subtle effects lower doses physiology exist. extent efficacy low-dose inhibitor treatment resulting death currently present critical issue oncology. prospect dose reduction promising as protocols at higher side effects. We assessed cycle changes induced by (paclitaxel, nocodazole vinorelbine) human lymphoid B-cell lines broad range. All had similar accumulation demonstrated “trigger” concentrations G2/M phase. Concentrations slightly below promoted sub-G1 Multi-label analysis live showed population heterogeneous may include still viable after 24 hours treatment. Effects observed were for expressing Tat-protein. Thus progression differentially affected low concentrations.

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