循環農業：農業廢棄物再資源化【食品暨應用生物科技學系/蔣恩沛特聘教授】
| 論文篇名 | 英文：Treatment of 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 inhibits TNF-alpha-mediated expression of MMP-9 protein and cell invasion through the suppression of JNK pathway and microRNA 221 in human pancreatic adenocarcinoma cancer cells 中文：13-順式視黃酸與 1,25-二羥基維生素 D3 治療通過抑制人胰腺癌細胞中的 JNK 路徑和microRNA 221抑制TNF-α介導的MMP-9蛋白表達和細胞侵襲 |
| 期刊名稱 | PLoS One |
| 發表年份,卷數,起迄頁數 | 2021, 16, e0247550 |
| 作者 | Cheng, Yen-Huang; Chiang, En-Pei Isabel(蔣恩沛); Syu, Jia-Ning; Chao, Che-Yi; Lin, Hung-Yu; Lin, Cheng-Chieh; Yang, Mei-Due; Tsai, Shu-Yao; Tang, Feng-Yao* |
| DOI | 10.1371/journal.pone.0247550 |
| 中文摘要 | 人胰腺導管腺癌 (PDAC) 是一種致命的癌症類型，死亡率非常高。發炎性細胞因子如腫瘤壞死因子-α (TNF-α) 在 PDAC 的進展中起關鍵作用。最近，通過預防劑抑制細胞侵襲在預防轉移性腫瘤方面受到了相當大的關注。多項臨床研究表明，脂溶性維生素 (如維生素 A 和維生素 D) 的天然形式或類似物可以作為抗癌劑來抑制癌症的發展。本研究中，我們的結果表明，13-順式視黃酸 (13-順式 RA) 與 1,25-二羥基維生素 D3 (1,25-VD3) 的共同處理顯著抑制 PDAC 體外 TNF-α 介導的細胞侵襲。13-cis RA 與 1,25-VD3 的共同處理還通過阻斷 c-Jun N-末端激酶 (JNK) 和核因子 kappa B (NF-κB) 信號通路。我們的結果表明，TNF-α 的處理導致組織抑製劑金屬蛋白酶-3 (TIMP-3) 蛋白的表達降低，並通過人類 PDAC 細胞中 microRNA-221 (miR-221) 的上調誘導 MMP-9 蛋白與細胞侵襲。此外，SP600125 (JNK 通路的特異性抑製劑) 的處理或 13-順式 RA 和 1,25-VD3 的共同處理顯著誘導 miR-221 的表達降低和 TIMP-3 蛋白的表達增加。這些結果表明 13-cis RA 與 1,25-VD3 顯著抑制 TNF-α 介導的細胞侵襲，因此具作為 PDAC 預防劑的潛力。 |
| 英文摘要 | Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received considerable attention in the prevention of metastatic tumors. Several clinical studies suggested that natural forms or analogues of fat-soluble vitamins such as vitamin A and vitamin D can work as anti-cancer agents to inhibit the development of cancer. In this study, our results demonstrated that co-treatment of 13-cis retinoic acid (13-cis RA) and 1,25-dihydroxyvitamin D3 (1,25-VD3) significantly inhibited TNF-α mediated cell invasion in PDAC in vitro. Cotreatment of 13-cis RA and 1,25-VD3 also inhibited TNF-α mediated expression of matrix metalloproteinase-9 (MMP-9) protein through blocking c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB) signaling pathways. Our results demonstrated that treatment of TNF-α lead to a decreased expression of tissue inhibitor of metalloproteinase- 3 (TIMP-3) protein and an induction of MMP-9 protein and cell invasion through an upregulation of microRNA-221 (miR-221) in human PDAC cells. Moreover, treatment of SP600125 (a specific inhibitor of JNK pathway) or cotreatment of 13-cis RA and 1,25-VD3 significantly induced a decreased expression of miR-221 and an increased expression of TIMP-3 protein. These results suggest that 13-cis RA and 1,25-VD3 significantly suppress TNF-α mediated cell invasion and therefore potentially act as preventive agents against PDAC. |
| 發表成果與本中心研究主題相關性 | 代謝路徑追蹤之應用 |
