柚皮素對HBx誘導肝癌細胞轉移之影響

柚皮素是一種大量存在於水果、蔬菜和中草藥中的黃酮類化合物，具有很強的抗增殖特性和誘導肝癌細胞凋亡的能力。然而，尚未研究柚皮素對預防HBx誘導的肝癌細胞侵襲的作用。方法：為了確定HBx是否調節遷移，侵襲和生長因子的表達，我們女，將檢驗HBx和HBx-GFP融合蛋白是否在用或不用DOX處理的HBx轉染細胞中表達。結果：柚皮素通過抑制激活蛋白（AP）-1和核因子-κB（NF-κB）活性抑制MMP-9轉錄，並通過抑制細胞外磷酸化抑制TPA誘導的AP-1活性。信號相關激酶（ERK）和c-Jun N末端激酶（JNK）信號通路。柚皮素還通過IκB抑制HBx誘導的NF-κB核轉位抑制。結論：這些數據表明，柚皮素通過抑制多種信號傳遞導途徑抑制肝細胞癌的侵襲性和轉移潛能。因此，柚皮素可具有抑制肝細胞癌侵襲和轉移的治療潛力，並且可作為全身治療的潛在用藥。

關鍵字

柚皮素； HBx ；基質金屬蛋白酶9 ；血管內皮生長因子；腫瘤侵襲

並列摘要

Background:Naringenin, a flavonoid abundantly presents in fruits, vegetables, and in Chinese herbs, possesses strong anti-proliferative properties and the ability to induce apoptosis on hepatoma cell lines. However, the effects of Naringenin on preventing HBx-induced invasion of hepatoma cells have not been studied. Methods:To determine whether HBx modulates migration, invasion, and the expression of growth factors, we examined whether HBx and the HBx-GFP fusion protein were expressed in HBx-transfected cells treated with or without DOX. Results:Naringenin suppressed MMP-9 transcription by inhibiting activator protein (AP)- 1 and nuclear factor-κ B (NF-κB) activity and suppressed TPA-induced AP-1 activity through inhibition of phosphorylation in the extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways. Naringenin also suppressed Hbx-induced inhibition of NF-κB nuclear translocation through IκB. Conclusions:These data suggest that naringenin suppresses the invasiveness and metastatic potential of hepatocellular carcinoma cells by inhibiting multiple signal transduction pathways. Naringenin thus may have the therapeutic potential to inhibit the invasion and metastasis of hepatocellular carcinoma and act as a potential drug for systemic therapies.

並列關鍵字

Naringenin ； HBx ； Matrix metalloproteinase 9 ； VEGF ； Tumor invasion

參考文獻

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柚皮素對HBx誘導肝癌細胞轉移之影響

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