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. 2019 Nov 12;9:16647. doi: 10.1038/s41598-019-53145-x

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© The Author(s) 2019

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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Effects of the therapy on the pathways related to the signaling downstream of insulin receptors. A proposed graphical mechanism illustrates the possible anti-tumor effect of insulin and chemotherapeutic agents in colon cancer cells. Insulin binds to its receptor and initiates a cascade of intracellular processes. Insulin may enhance the therapeutic effect of anticancer drugs through the downregulation of GRB2, a crucial substrate for cell cycle advancement and cell motility, as well as PIK3CA, which plays a pivotal role in growth, proliferation, survival, and migration of cancer cells. *Downregulated after the treatment with cytotoxic agent alone and in combination with insulin. **Downregulated only in insulin pretreated cells.