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. 2023 Aug 9;30(10):1414–1425. doi: 10.1038/s41417-023-00648-5

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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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — A–E The cells were treated with cetuximab at 10 or 20 μg/ml cetuximab for four days. A The response of HCT116 (KRAS^G13D/-) and HCT116 (KRAS^wt/-) cells to cetuximab. B The response of DLD-1(KRAS^G13D/-) and DLD-1(KRAS^wt/-) cells to cetuximab. C The response of RKO (BRAF^V600E/-/-) and RKO (BRAF^wt/-/-) cells to cetuximab. D The response of HT29(BRAF^V600E) cells transfected with or without shRNA targeting BRAF to cetuximab. E The response of Caco-2-CR and Caco-2 cells to cetuximab. F The dose-response curve and IC⁵⁰ of 3-BP in HCT116 (KRAS^G13D/-), HCT116 (KRAS^wt/-), DLD-1(KRAS^G13D/-) and DLD-1 (KRAS^wt/-) cells. G The dose-response curve and IC⁵⁰ of 3-BP in RKO (BRAF^V600E/-/-), RKO (BRAF^wt/-/-), HT29(BRAF^V600E), and HT29(shBRAF) cells. H The dose-response curve and IC⁵⁰ of 3-BP in Caco-2 and Caco-2-CR cells. I The Comparison of the IC⁵⁰ values between cetuximab-resistant cell lines and their corresponding cetuximab-sensitive cell lines. (J–L) The cell viability after the treatment of 5 μM 3-BP and/or 10 μg/ml cetuximab for four days in DLD-1(KRAS^G13D/-) cells (J), HT29(BRAF^V600E) cells (K) and Caco-2-CR cells (L). M The cells were exposed to 5 μM 3-BP and/or 10 μg/ml cetuximab for two weeks, and the colony formation was evaluated. N–P The xenograft nude mouse models, DLD-1(KRAS^G13D/-) (N), HT29(BRAF^V600E) (O), and Caco-2-CR (P), were established. The tumor-bearing mice were treated with PBS (0.2 ml), 3-BP (4 mg/kg/day, dissolved in 0.2 ml PBS), cetuximab (50 mg/kg/day, dissolved in 0.2 ml PBS), or the co-treatment of both 3-BP and cetuximab. The volumes and tumor weights were evaluated. Data are expressed as mean ± SD, n = 3 biological replicates in (A–H), (J–L), and n = 5 biological replicates in (M–P). *P < 0.05, **P < 0.01, ns: not significant.