| 摘要: | 表沒食子兒茶素沒食子酸脂（(-)-epigallocatechin-3-gallate（EGCG））已被發現有許多益處，如：化學防治活性、抗癌活性與抗氧化活性等，但對於頭頸部癌細胞（HNSCC）的影響還未被清楚的研究。從多種黃酮類、多酚類的天然化合物中，我們發現EGCG明顯的抑制頭頸部癌細胞的生長。
根據研究指出癌細胞中持續活化的STAT3和癌細胞的存活、增生是有相關性的。且在眾多癌症病患中，大於90%比例的口腔癌病患中可以發現STAT3被過度活化的現象，此情形在其他的癌症病患中卻非如此。使我們想探究EGCG對頭頸部癌細胞株的抑制活性，是否跟STAT3有所關聯? 在我們使用四株頭頸部癌細胞株(SAS、Cal-27、Ca9-22、HSC3) ，進一步的研究EGCG 對於頭頸部癌細胞中STAT3訊息傳遞路徑的影響，發現EGCG抑制STAT3磷酸化的效果與給藥劑量、給藥時間有著依存性的關係；在細胞層面的觀察裡， STAT3磷酸化表現量逐漸下降； 在處理EGCG後，STAT3明顯的移動至細胞核外；STAT3路徑下游蛋白表現量也下降。
interleukin-6 (IL-6)可藉由磷酸化訊息蛋白singal transducer and activator 3 (STAT3)而促進腫瘤細胞的存活與生長。頭頸部癌細胞株會自體分泌IL-6刺激自身的STAT3活化。我們發現EGCG可以消除IL-6在頭頸部癌細胞中誘導STAT3活化的能力，更進ㄧ步的抑制IL-6 所誘導的細胞增生現象。在與Apigenin、Curcumin、AG490比較抑制IL-6 所誘導的細胞增生中，EGCG也是最有效的抑制者。
總結而論，我們實驗的結果強烈的指出EGCG是一個有潛力去抑制IL-6誘導STAT3磷酸化的抑制劑，而此機轉可反應出EGCG抑制口腔癌細胞增生的原因。
Many beneficial properties have been attributed to (-)-epigallocatechin-3-gallate (EGCG), including chemopreventive, anticarcinogenic, and antioxidant active. The antitumor effect of green tea compound EGCG have not been studied clearly in head and neck squamous cell carcinoma cells.
Previous study indicated that the constitutive activation of singal-transducer-and-activator-3 (STAT3) were associated with the proliferation of HNSCC cells.
Numerous reports suggest that interleukin-6 (IL-6) promotes survival and proliferation of tumor cells through the phosphorylation of STAT3. Constitutive of STAT3 in HNSCC was relative with its proliferation and survival. Thus, compound that can suppress STAT3 activation have potential for the treatment of HNSCC.
Therefore, we examined in detail the molecular effect of EGCG on four HNSCC cell lines, SAS, Cal-27, Ca9-22 and HSC3. In the beginning, we found the great inhibition on HNSCC cells of EGCG. Further, we focused the effect of EGCG on STAT3 signal pathway. In this study, the 70% lethal dose (IC70) of EGCG for three cell lines, SAS, Cal-27 and Ca9-22, was 20 μM, and EGCG inhibited STAT3 phosphorylation in a dose- and time- dependent manner. Nuclear translocation of STAT3 was also inhibited by EGCG. Besides inhibiting constitutive expression, EGCG also abrogated the IL-6-induced activation of STAT3 and further inhibited IL-6-induced proliferation on HNSCC cell. Compare with Apigenin, Curcumin and AG490, EGCG was more effective inhibitor of IL-6-induced proliferation on HNSCC cells.
Overall, our results strongly suggest that EGCG is a potent inhibitor of constitutive and IL-6-induced STAT3 phosphorylation. This mechanism may be at least partially responsible for EGCG’s ability to suppress proliferation of HNSCC cells. Taken together, these finding suggest that this naturally occurring compound may be useful, in the chemoprevention and/or treatment of HNSCC. |
