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. 2021 Mar 9;40:91. doi: 10.1186/s13046-021-01892-z

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — Combination treatment of defactinib with paclitaxel shows synergistic lethality in vitro and in vivo. a. Combination index was calculated after treatment of cells (Suit-2, PDAC-1, PDAC-3) with IC25 or IC50 of defactinib in combination with a range of paclitaxel dosing. Combination treatment showed strong synergistic effects in PDAC-1 and synergistic/additive effect in two other cell lines. b. Example of drug curves of primary cell line PDAC-1of defactinib in combination with paclitaxel. c. LC-MS measurement (n = 2) of drug concentration of cells (PDAC-1) exposed to defactinib/paclitaxel/combination showed highest intracellular concentrations of defactinib with combination. d. Polymerized tubulins were significantly highest in PDAC-1 cells treated with combination exposure to monotreatment. e. Growth of tumor size (defined as BLI in pancreas region) was significantly inhibited from day 23 to 31 in the nab-paclitaxel and combination group (multiple t-test, corrected for multiple testing by Holm-Sidak test)