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. 2022 Nov 30;12:1021632. doi: 10.3389/fonc.2022.1021632

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Copyright © 2022 Prasopporn, Suppramote, Ponvilawan, Jamyuang, Chanthercrob, Chaiboonchoe, More-Krong, Kongsri, Suntiparpluacha, Chanwat, Korphaisarn, Okada, Sampattavanich and Jirawatnotai

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The combination of LCL161 + GEM/CIS prevents the emergence of drug-resistant cells. (A–D) The emergence of multidrug-resistant TFK1 and KKU213C cells under various drug treatments. TFK1 and KKU213C cells were treated with GEM/CIS, LCL161, or LCL161 + GEM/CIS for 4 weeks, 8 weeks, or 10 weeks. Emerging colonies were stained with crystal violet and imaged. The number of emerging multidrug-resistant clones in 96-well plates are shown in images B–D. (E, F) The effectiveness of triplet combination and sequential regimen is compared in TFK1R and KKU213R cells. Multidrug-resistant cells were stained with crystal violet and imaged every 5 days. (G, H) The effectiveness of the triplet therapy in TFK1, TFK1R, KKU213C, and KKU213CR cells with and without drug holiday. Cells were treated with LCL161, GEM/CIS, or LCL161 + GEM/CIS and stained with crystal violet at the indicated time points.