臺灣博碩士論文加值系統

關於口腔癌的致病機轉，較多研究是將重點放在化學因子所誘發的細胞增生與惡化，然而物理性刺激亦可能是誘發的原因。機械性刺激與癌症的關係，在乳癌、口腔癌方面有想當多的研究。以往，建構體外的癌細胞3D培養系統是利用Matrigel作為基材，本研究則是以微生物多醣體Gellan gum水膠，建構3D培養系統。Gellan gum利用二價陽離子凝膠機制，製備0.6% 及0.8% 之Gellan gum與0.5% 之CaCl2 凝膠成為3D結構，並與口腔癌細胞SCC15 (squamous cell carcinoma 15)共同培養形成腫瘤球體。由WST-1試驗初步的實驗結果顯示於3D及2D培養24 hrs、48 hrs及72 hrs後材料對口腔癌細胞SCC15不影響其細胞活性。另外，Gellan gum的3D水膠亦被利用作為脂溶性藥物和水溶性藥物的傳輸載體。由研究結果證實，Gellan gum水膠作為水溶性藥物的傳輸載體，3D結構在48小時就會崩解；包覆脂溶性藥物，Gellan gum的結構則可以維持超過2週。本研究成果，未來將應用在口腔癌的體外研究平台與口腔癌的治療。

About oral cancer pathogenesis, more research is focused on the chemical factor induced cell proliferation and progression, however, physical stimulation may also induce reasons. Relations mechanical stimulation and cancer in breast cancer, oral cancer aspects have wanted more research. In the past, construction of 3D culture system of cancer cells in vitro using Matrigel as a substrate, this study is based on microbial polysaccharides Gellan gum hydrogel to construct 3D cell culture system. Gellan gum form gels with divalent cations, preparation of 0.6% and 0.8% of Gellan gum with 0.5% CaCl2 to become a 3D structure of the gel, and co-cultured with the oral cancer SCC15 (squamous cell carcinoma 15) to form tumor sphere. By WST-1 test preliminary experimental results are shown in 3D and 2D culture 24 hrs, 48 hrs and 72 hrs after, materials for oral cancer SCC15 has no significant differences. In addition, the 3D hydrol gel was also used as a fat-soluble drugs and water-soluble drugs of drug transport carrier. Confirmed by the findings, Gellan gum gum as water soluble drug transport vector, 3D structures will disintegrate in 48 hours; Encapsulating of a lipophilic drug, Gellan gum structure can be maintained over two weeks. The research results will be applied in the future of the in vitro research platform and oral cancer treatment.

目錄
論文電子檔著作權授權書 i
論文口試委員審定書 ii
摘要 iii
Abstract iv
圖目錄 viii
表目錄 x
第一章 緒論 1
1.1 口腔癌流行病學 1
1.2 口腔鱗狀細胞癌(squamous cell carcinoma,SCC)致病機制 2
1.2.1 生化機轉 2
1.2.2 化學性刺激癌化機轉 4
1.2.3 物理性刺激癌化機轉 5
1.3 水膠的交聯方式 9
1.4 3D腫瘤球體(3D tumor spheroids)在癌細胞研究之應用 11
1.5 Gellan gum物化性質及凝膠特性 16
1.6 以Gellan gum作為藥物基材釋放之研究 19
1.6.1 藥物控制釋放系統的優點 22
1.6.2 藥物動力學(Pharmacokinetics)概論 23
1.6.3 藥物動力學定義 24
1.6.4 不同性質的藥物在藥物釋放上之差異 25
研究動機 26
第二章 藥品 27
第三章 實驗方法 29
3.1 水膠之製備 29
3.2 水膠之機械強度測試 30
3.3 口腔癌細胞株SCC15之培養 31
3.4 3D培養模式 33
3.5 水膠之型態(SEM) 34
3.6 WST-1細胞增生試驗 35
3.7 冷凍切片及HE染色 37
3.8 水膠之藥物傳輸測試 38
第四章 實驗結果與討論 40
4.1 水膠之機械強度測試 40
4.2 3D培養模式 47
4.3 水膠之型態(SEM) 50
4.4 WST-1細胞活性試驗 51
4.5 HE染色 52
4.6 水膠之藥物傳輸測試 54
第五章 結論 58
參考文獻 61

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