三陰性乳癌（triple-negative breast cancer, TNBC）屬侵襲性組織學亞型乳癌，其動情激素受體（estrogen receptor, ER）、黃體激素受體（progesterone receptor, PR）和HER2 / neu受體的檢測均呈陰性，在治療上有很大的侷限。研究顯示表皮生長因子受體（epidermal growth factor receptor, EGFR）酪氨酸激酶抑製劑（tyrosine kinase inhibitor, TKI）可抑制TNBC的增殖，然而在臨床治療中卻發現其成效不佳。原因之一可能與癌細胞和其相鄰基質細胞間的互動有關。例如癌症纖維母細胞會藉由分泌肝細胞生長因子（hepatocyte growth factor, HGF）結合癌細胞上的 Met 受體，進而降低 TKI 對 TNBC 的療效，顯示微環境對癌細胞的發展有著關鍵性的影響。為了尋找有效的 TNBC 抑製劑，本篇研究建立了一個以纖維母細胞共同培養的洋菜膠腫瘤細胞群落形成試驗，以測試乳癌細胞 MDA-MB-468 的腫瘤生成。實驗中測試了費氏麴菌萃取物對 TNBC 的抑制活性，結果發現費氏麴菌之二次代謝產物可抑制纖維母細胞所調節之 MDA-MB-468 腫瘤細胞群落生成。進一步的研究發現其中一個代謝物對 EGFR 和 Met 的磷酸化具有抑制的活性，可為治療 TNBC 的潛力化療藥物。 Triple-negative breast cancer （TNBC）, which is tested negative for estrogen receptor, progesterone receptor and HER2 / neu receptor, is an aggressive histological subtype of breast cancer with limited choice of treatments. Epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） have been studied to inhibit proliferation of TNBC, however, they lacked efficacy in clinical treatment. This may be due to cross-talk between cancer cells and neighboring stromal cells. For example, hepatocyte growth factor （HGF） secreted by cancer-associated fibroblasts has been shown to bind to a Met receptor and reduce efficiency of TKIs in TNBC, indicating that microenvironment affected development of cancer cells. To survey the effective TNBC inhibitors, I established a soft agar colony formation system for breast cancer MDA-MB-468 cells with co-culture of fibroblasts. Neosartorya fischeri extracts were tested for their inhibitory activity on TNBC by applying to this system. The results showed that some secondary metabolites of Neosartorya fischeri inhibited fibroblast-mediated colony formation of MDA-MB-468 cells. One of these metabolites exhibited inhibitory effect on phosphorylation of EGFR and Met, which offered the potential as a chemotherapeutic agent for TNBC.
