基因調控層面探討黃酮類天然中草藥作為抗口腔癌藥物可行性研究;Feasibility of flavonoid natural Chinese herbal medicines as anti-oral cancer drugs of gene regulation

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Title:	基因調控層面探討黃酮類天然中草藥作為抗口腔癌藥物可行性研究;Feasibility of flavonoid natural Chinese herbal medicines as anti-oral cancer drugs of gene regulation
Authors:	黃詣超;Huang, Yi-Chao
Contributors:	系統生物與生物資訊研究所
Keywords:	口腔癌;化學治療;中草藥;黃酮類藥物;基因表達;輔助治療;Oral cancer;chemotherapy;Chinese herbal medicine;flavonoid;gene expression;adjuvant treatment
Date:	2023-08-11
Issue Date:	2024-09-19 15:51:40 (UTC+8)
Publisher:	國立中央大學
Abstract:	口腔癌是全球十大癌症之一，全球口腔癌發病率呈上升趨勢，且有年輕化趨勢，給全球帶來醫療健康沉重的負擔，在口腔癌的發病率和死亡率居高不下的情況下，有90%是由口腔鱗狀上皮細胞癌造成的，有76%的口腔癌患者在5年內存活且無轉移，但發病率仍然持續上升。口腔癌有多種治療選擇，包括手術、放射療法和化學療法，但副作用相當的大，尤其以手術方式進行治療更是補可逆的治療方式，所以本篇論文主要探討利用天然中草藥開發治療口腔癌的藥物。口腔癌的發生是因為相關特定基因突變造成，我們試著利用中草藥對口腔癌細胞的基因影響來探討中草藥開發成為口腔癌藥物的可行性，本篇論文探索27種化療藥物及63種天然化合物發現大部分藥理作用主要是透過誘發口腔癌凋亡途徑達到抑制口腔癌細胞生長的效果，並且發現黃酮類的天然中草藥化合物可以作為抗口腔癌藥物發展的可行性，所以本篇論文要探索芫花萃取物HGK在口腔癌細胞中特定基因突變的治療機轉。 Hydroxygenkwanin (HGK) 是一種從瑞香中提取的天然黃酮類化合物。以往的研究發現HGK具有抗發炎、抗癌效果，但在口腔癌的作用仍不清楚，本篇論文以HGK黃酮類的中草藥作為發展天然中草藥確實會影響癌細胞基因表達作為論述。實驗證明HGK 劑量會抑制 SAS 和 OCEM1 細胞的生長。在基因功能富集分析顯示了細胞運動、細胞週期和細胞生長和增殖的重要途徑。我們透過流式細胞技術證明了 HGK 誘導細胞週期停滯，利用生物技術證實HGK抑制細胞聚落形成能力和細胞運動。Western blot顯示HGK通過p21激活誘導細胞週期停滯並引起內在細胞凋亡途徑。HGK通過下調Vimentin蛋白抑制細胞侵襲和遷移，HGK 可望成為治療口腔癌的天然中草藥。過去很多研究探討中草藥對癌細胞的作用，但沒有針對癌細胞的基因表達特別闡述，我們希望藉由HGK作用口腔癌細胞的基因表達，藉以探討開發天然抗口腔癌藥物是提供一種降低口腔癌治療風險和開發口腔癌輔助治療的可能性。 ;Oral cancer is one of the top ten cancers worldwide. The global incidence of oral cancer is increasing and tends to occur at a younger age, placing a heavy burden on global medical health. Of the high incidence and mortality of oral cancer, 90% is caused by oral squamous cell carcinoma and 76% of oral cancer patients survive within 5 years without metastasis, but the incidence rate continues to rise. There are many treatment options for oral cancer,including surgery, radiotherapy and chemotherapy, but the side effects are quite large, especially surgical treatment is a non-reversible treatment, so this thesis mainly discusses the use of natural Chinese herbal medicine to develop the treatment of oral cancer. The occurrence of oral cancer is caused by related specific gene mutations. We are trying to use the influence of Chinese herbal medicines on the genes of oral cancer cells to explore the feasibility of developing Chinese herbal medicines into oral cancer drugs. In this thesis, 27 chemotherapeutic drugs and 63 natural compounds are investigated. Most of the pharmacological effects are mainly to inhibit the growth of oral cancer cells by inducing the apoptosis pathway of oral cancer, and found that the flavonoids of natural Chinese herbal compounds can be used as anti-oral cancer drugs, so this paper will explore Daphne genkwa extract therapeutic mechanism of HGK in specific gene mutations in oral cancer cells. Hydroxygenkwanin (HGK) is a natural flavonoid extracted from Daphne. Previous studies have shown that HGK has anti-inflammatory and anticancer effects, but its role in oral cancer is still unclear. This paper discusses that HGK flavonoids, as natural Chinese herbal medicines, can indeed affect the gene expression of cancer cells. Experiments showed that HGK dosage inhibited the growth of SAS and OCEM1 cells. Functional enrichment analysis of genes revealed important pathways for cell motility, cell cycle, and cell growth and proliferation. We demonstrated by flow cytometry that HGK induces cell cycle arrest and by bioassay that HGK inhibits cell colony formation and cell motility. Western blot showed that HGK induces cell cycle arrest and induces the intrinsic apoptotic pathway through p21 activation. HGK inhibited cell invasion and migration by downregulating Vimentin protein. HGK may be an effective natural product for the treatment of oral cancer. In the past, many studies have investigated the effect of Chinese herbal medicine on cancer cells, but they have not looked specifically at the gene expression of cancer cells. We hope that through the effect of HGK on the gene expression of oral cancer cells, it will be possible to explore the development of natural anti-oral cancer drugs to provide a treatment for oral cancer. Risk and possibility of developing adjuvant therapy for oral cancer.
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