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. 2021 Jan 19;40:34. doi: 10.1186/s13046-021-01831-y

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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. 7 — Vitamin C inhibit the feedback activation of MAPK/ERK pathways in a ROS dependent way. a The indicated cells were treated with PLX4032 4 μM, Vitamin C 0.5 mM (VC) with or without NAC 0.5 mM for 24 h, and cell lysates were then subjected to western blot analysis to determine the re-activation of MAPK/ERK pathways (upper panels). The normalized band intensity of Pan-AKT and pERK were shown in lower panels, tERK was used for normalizing pERK. b Treating BRAF^MT thyroid cancer with simple PLX4032 will induce a feedback activation of MAPK/ERK as well as PI3K/AKT pathways, leading to the drug resistance and cell survival. c When we combined Vitamin C and PLX4032, the feedback activation was inhibited by Vitamin C due to the accumulation of ROS, leading to the death of cancer cells. Data were presented as mean ± SD. ns, not significant; ***/^^^/###, P < 0.001. ns: compared with control group; *: compared withPLX4032 + VC group; ^: compared with VC group; #: compared with PLX4032 group