FLLL32誘導人類口腔癌細胞凋亡的分子機制

口腔癌是台灣常見且重要之癌症。現有的治療方式以手術、放射治療、化療、標靶治療為主，但仍造成預後不佳和復發現象。 FLLL32是薑黃素 (curcumin) 的衍生物，具有抗腫瘤活性的能力。目前已知FLLL32可以誘導黑色素瘤細胞凋亡，也能抑制胰臟癌、乳癌和神經纖維瘤的腫瘤生長，然而FLLL32對於口腔癌的影響尚未釐清。因此本篇研究將探討FLLL32在口腔癌中是否誘導細胞凋亡與其分子機制。我們觀察到FLLL32在口腔癌細胞 (SCC-9, HSC-3 cell lines) 中抑制細胞生長。透過Flow Cytometry的結果，發現FLLL32可以使細胞週期停滯在G2/M，此外我們透過Annexin-V/PI雙染發現FLLL32誘導口腔癌細胞凋亡。在人類細胞凋亡分析 (Human apoptosis array) 觀察到FLLL32在SCC-9、HSC-3細胞中促使cleaved caspase-3及HO-1的表現增加。在凋亡相關分子機制上，FLLL32活化caspase-8, caspase-9, caspase-3等凋亡蛋白與mitogen-activated protein kinase (MAPK) 路徑蛋白。接著使用相關抑制劑驗證其透過p38 MAPK訊息傳遞路徑誘導口腔癌細胞凋亡的發生。綜合上述結果，我們證實FLLL32可以抑制口腔癌細胞生長並誘導細胞凋亡。

Oral cancer is the most common oral malignant tumors in Taiwan. The existing treatment has a lot of methods, including surgery, radiation therapy, chemotherapy and target therapy. But still cause poor prognosis and recurrence. FLLL32, a synthetic analogue of curcumin with anti-tumor activity, has currently known to induce melanoma apoptosis and inhibit tumor growth in many cancers. However, the mechanisms of FLLL32 on oral cancer have not yet been clarified. In this study, we will explore whether FLLL32 induces apoptosis in oral cancer. First, we determined that FLLL32 can inhibit cell viability of oral cancer. Next, we analyzed the effect of FLLL32 on cell cycle in oral cancer cells and observed that the G2/M phase was increased. Additionally, Annexin-V/PI double staining revealed that FLLL32 induced apoptosis in oral cancer. FLLL32 increase the expression of cleaved caspacse-3 and HO-1 in oral cancer cells in Human apoptosis analysis. FLLL32 activates apoptosis proteins such as caspase-8, caspase-9, caspase-3 and mitogen-activated protein kinase (MAPK) pathway proteins in apoptosis-related molecular mechanisms. Using MAPK inhibitors to verify that FLLL32 induced apoptosis of oral cancer cells through the p38 MAPK signaling pathway. In conclusion, we have confirmed that FLLL32 inhibits the cell growth and induces apoptosis of oral cancer cells.