IL-1β為一種促發炎性細胞激素，與腫瘤形成有很大的相關性，可作為一個癌症進展的指標。此外，EGFR過度表現時與腫瘤生長及轉移也有很大的相關。在我們研究中發現有EGFR過度表現現象的人類子宮頸上皮細胞癌A431中，處理EGF之後，IL-1β基因與蛋白表現，有上升的情形。然而，在細胞中EGF是如何調控IL-1β基因表現的，仍不清楚。首先我們確認EGF是經由轉錄作用，而非影響IL-1β mRNA穩定度，進而誘導IL-1β基因表現。我們更利用Akt藥理性抑制劑LY294002與NF-κB藥理性抑制劑確認EGF經由Akt-NF-κB訊息傳遞路徑，來誘導IL-1β基因啟動區活性。接著利用免疫螢光染色法，確認EGF會活化Akt訊息傳遞路徑而誘導NF-κB (p65)的入核現象；下一步，由DNA親和沉澱實驗得知，EGF活化Akt路徑後，再促使NF-κB (p65)入核結合到IL-1β啟動區上的NF-κB結合位上，進而活化IL-1β啟動區的活性。此外，我們另外發現另一個轉錄因子ARNT也參與在EGF所誘導的IL-1β基因調控中。最後我們發現EGF可以藉由增加IL-1β，而降低了cisplatin對於癌細胞的毒殺作用，進而增加細胞的抗藥性。總結整篇研究得知在癌細胞中EGF藉由活化Akt- NF-κB 路徑而使IL-1β表現增加，進而影響化療藥物的抗藥性，因此IL-1β的表現量可作為評估藥物於癌症治療效用的重要指標。

IL-1β is the well-known cytokine that has been characterized as an indicator of several cancers, and it may affect the process of carcinogenesis. In addition, epidermal growth factor receptor (EGFR) is an important regulator of tumor growth and metastasis. We found that IL-1β gene and protein expression were induced by treating EGFR-overexpressed A431 cell with EGF. However, the mechanism involved in EGF-regulated IL-1β expression is not clarified in A431 cells. IL-1β was found to be induced by EGF which was mediated through the transcription activation, but not change of mRNA stability. The involvement of Akt and NF-κB signaling pathways in the EGF-induced IL-1β gene expression and promoter activity was ensured by treating cells with Akt and NF-κB inhibitors, LY294002 and Parthenolide, respectively. By Immunofluorescence staining assay, we found that EGF-stimulated nuclear transclocation of NF-κB (p65) was inhibited by pretreating cells with LY294002 and Parthenolide. Furthermore, by DNA affinity precipitation assay we also found that EGF increased the binding of NF-κB to NF-κB binding site of IL-1β promoter through activation of Akt pathway, and then activated IL-1β promoter activity. In addition, a transcription factor, ARNT, was participated in regulation of EGF-induced IL-1β gene expression. Furthermore, we found that EGF could regulate cancer cells resistance to cisplatin through the induction of IL-1β expression. These results reveal that up-regulation of IL-1β by EGF-activated Akt-NF-κB pathway in cancer cells can confer resistance to chemotherapy. The expression of IL-1β may become a biomarker to evaluate the successful cancer treatment.

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