Abstract 83: Irinotecan resistance in type 2 interleukin-1 receptor overexpressed colorectal cancer cells is overcome by inhibitor of MEK
| Autor: | Te-Chang Lee, Chun-Ho Chu, Ai-Chung Mar |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Cancer Research. 77:83-83 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2017-83 |
| Popis: | We have previously demonstrated that the expression of interleukin-1 receptor type II (IL1R2) is closely associated with the advanced staging and distant metastasis in patients with CRC. We also found that enhanced expression of IL1R2 played certain roles to resist the targeted therapeutics, regorafenib, in CRC cells. Whether IL1R2 expression is associated with the resistance to chemotherapeutics is unclear. Irinotecan, a water-soluble and semisynthetic derivative of camptothecin, is one of widely used first- and second-line chemotherapeutics for treatment of patients with metastatic colorectal cancer (CRC). Herein, we first demonstrated that enhanced expression of IL1R2 resulted in increased resistance of CRC cells to irinotecan using IL1R2 ectopically expressed HCT116 and DLD-1 cells, which were IL1R2 low expressing CRC cells, and IL1R2 silenced HT29 cells, which were IL1R2 high expressing CRC cells. Since we have shown that IL1R2 may activate MEK/ERK signaling by inhibition of PP2A, we further revealed that a specific inhibitor of MEK, CI-1040, could overcome the irinotecan resistance in IL1R2-overexpressing DLD-1 and HT29 cells. Our result showed that the combination of irinotecan and CI-1040 synergistically suppressed the cell growth in high IL1R2 expressing CRC cells but less significant in low IL1R2 expressing cells. We also confirmed that treatment of IL1R2-overexpressing CRC cells with CI-1040 significantly suppressed the pERK, a downstream target of MEK. These results support that IL1R2 mediates through activation of MEK/ERK signaling to cause irinotecan resistance in human CRC cells. The investigation how IL1R2 induces irinotecan resistance is ongoing. Accordingly, we may suggest that combined treatment of irinotecan and MEK-ERK inhibitor is a potential therapeutic strategy against IL1R2 overexpression related irinotecan resistant CRC. Citation Format: Ai-Chung Mar, Chun-Ho Chu, Te-Chang Lee. Irinotecan resistance in type 2 interleukin-1 receptor overexpressed colorectal cancer cells is overcome by inhibitor of MEK [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 83. doi:10.1158/1538-7445.AM2017-83 |
| Databáze: | OpenAIRE |
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