白藜醇衍生物4-Bromo-Resveratrol於胃癌幹細胞化與抗藥性抑制作用之研究

The Study of Resveratrol Analog 4-Bromo-Resveratrol on Gastric Cancer Cell Stemness and Chemoresistance Inhibition

戴運生(Yun-Sheng Tai)

指導教授 ： 陳志毅

中山醫學大學/醫學院/醫學研究所/博士(2022年)

https://doi.org/10.6834/csmu202100313

摘要

胃癌是全球惡性腫瘤和癌症相關死亡的最常見原因，而癌幹細胞被定義為腫瘤中具有啟動腫瘤生長和維持自我更新以及轉移潛力的獨特亞群。化學治療是胃癌治療的選項之一，但目前可用的治療藥物療效有限。過去研究顯示胃癌幹細胞可能在化療抗藥性中起關鍵作用，因此迫切需要選擇性標靶胃腫瘤中的胃癌幹細胞的新藥物。 而Sirtuin-3 (SIRT3) 是一種去乙酰化酶，可調節粒線體代謝穩定以維持膠質瘤幹細胞的特性。靶向粒線體蛋白 SIRT3 可能可為胃癌治療提供一種新的治療選擇。然而在胃癌中通過抑制 SIRT3 來調節胃癌幹細胞化的機制仍然未知。4-bromo-resveratrol (4-BR) 為白藜蘆醇的類似物，過去的研究指出4-BR能有效的抑制SITR3的表現。本研究中，我們評估了 SIRT3 抑制劑 4-BR對胃癌細胞幹細胞化的抑制能力。實驗結果發現4-BR 能透過 SIRT3-JNK訊息傳遞路徑來抑制胃癌細胞幹細胞化，4-BR可能具有未來胃癌幹細胞標靶治療的潛力。

關鍵字

白藜蘆醇衍生物 ； 胃癌 ； 胃癌幹細胞化 ； 化療敏感性

並列摘要

Chemotherapy is the treatment of choice for gastric cancer, but the currently available therapeutic drugs have limited efficacy. Studies have suggested that gastric cancer stem cells may play a key role in drug resistance in chemotherapy. Therefore, new agents that selectively target gastric cancer stem cells in gastric tumors are urgently required. Sirtuin-3 (SIRT3) is a deacetylase that regulates mitochondrial metabolic homeostasis to maintain stemness in glioma stem cells. Targeting the mitochondrial protein SIRT3 may provide a novel therapeutic option for gastric cancer treatment. However, the mechanism by which stemness is regulated through SIRT3 inhibition in gastric cancer remains unknown. We evaluated the stemness inhibition ability of the SIRT3 inhibitor 4-bromo-resveratrol (4-BR), an analog of resveratrol in human gastric cancer cells. Our results suggested that 4-BR inhibited gastric cancer cell stemness through the SIRT3-c-Jun N-terminal kinase pathway and may aid in gastric cancer stem-cell–targeted therapy.

並列關鍵字

4-bromo-resveratrol ； gastric cancer ； cancer stemness ； chemosensitivity

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