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. 2023 Sep 26;13:16144. doi: 10.1038/s41598-023-43498-9

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© The Author(s) 2023

Open Access This 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/.

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Colony formation assay of murine KC (A), PANC-1 (B), and MIA PaCa-2 (C) cells treated with 0.3 µM simvastatin (Sim), 0.05 mM metformin (Met), or a combination of both. Data are presented as scatter plots with bars (mean ± SD). **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001, ns = not significant. (D) Synergistic effects of metformin and simvastatin on inhibition of colony formation in PANC-1 cells were analyzed by isobologram analysis. The EC₅₀ of simvastatin and metformin were 0.45 µM and 0.25 mM, respectively. Red circles represent the EC₅₀ of metformin with simvastatin at 0.1 or 0.25 µM; their position under the isobole indicates a synergistic effect. Inset: Dose response of metformin (Met) without or with simvastatin (Sim).