根據統計，2007年台灣十大惡性腫瘤中，口腔癌排名第六，每年因口腔癌而死亡的人數高達上千人。癌細胞的局部侵犯與遠端轉移，是對癌症臨床治療的最大挑戰，而侵犯與轉移都和細胞的移動能力相關，其中影響細胞移動能力的最重要因素就是細胞骨架的重組。Gelsolin 是一種細胞骨架的調控蛋白，參與肌動蛋白 (actin) 的切割或是組裝，達成細胞骨架重新排列的功能。而且gelsolin 也參與調控細胞的型態維持、分化、以及凋亡等作用。然而，gelsolin也許具有更多未知的角色以影響細胞的作用。本研究的目的是探索gelsolin基因剔除對小鼠的影響，以及gelsolin與口腔癌生長還有細胞物理性質的關係。在本實驗中，過度表現gelsolin的口腔鱗狀上皮癌細胞株SCC9被成功建立，接著利用MTT assay分析不同的gelsolin表現量對SCC9細胞增生的影響，結果顯示gelsolin會抑制細胞的增生。相似的結果也同樣呈現在另一種口腔癌細胞OEC-M1，但是在利用RNAi方式抑制gelsolin表現量的口腔癌細胞株中卻沒有明顯的差異。利用直接計算細胞數量的方式也得到類似的趨勢。為了更進一步了解這種現象是否也真實發生在生物體內，我們在SCID老鼠身上誘導不同gelsolin表現量的腫瘤，結果顯示較慢的腫瘤生長速度會伴隨較高的gelsolin表現量，與細胞實驗有一致的結果。再者，利用原子力顯微鏡觀察活細胞並直接進行測量，發現gelsolin對細胞的物理特性有影響，較低的gelsolin表現量會使細胞有較堅硬的性質。我們也研究Gelsolin基因剔除對小鼠胚胎發育以及病理表現型的影響，發現gelsolin基因剔除小鼠有較高的風險發生腫瘤，也觀察到某些幼鼠出現發育遲緩的現象，此外，在所有老鼠以及發育第九天的胚胎中沒有發現同源基因剔除的基因型，顯示gelsolin可能參與了小鼠胚胎發育以及受精的過程。

Oral cancer is the sixth causes of death in 2007 among the ten major malignancies in Taiwan. Every year it makes thousands people die. Regional invasion and distant metastasis are great challenge for clinical cancer therapy. Both processes involved cell motility. Cytoskeleton remodeling is one of the most important factors associated with cell motility. Gelsolin is a cytoskeleton regulatory protein that severs or polymerizes actin. Gelsolin was also known to regulate cell morphology, differentiation, and apoptosis. Nevertheless, gelsolin may have other unknown roles in cellular processes. This study aimed to explore gelsolin’s functions in knockout animal and investigate their implications on oral cancer growth and biophysical properties. First of all, gelsolin over expression oral squamous cell carcinoma cell line model SCC9 was established. Then the MTT assay was used to analyze cell growth of SCC9 cells with different gelsolin expression levels. The result shows that gelsolin could inhibit cell proliferation, consistent with that of the OEC-M1 cells. However, no significant difference was observed in gelsolin knockdown cell lines. Direct cell count of cancer cell growth revealed a similar trend. In vivo tumor growth in SCID mice showed an association between slower tumor growth and high gelsolin expression level, consistent with in vitro results. Furthermore, atomic force microscope (AFM) force mapping in live cultured cells discovered a significant influence of gelsolin gene expression that low gelsolin expression convert toward higher cell rigidity. The effect of gelsolin in embryonic development and pathological phenotypes were also studied in gelsolin knockout mice. The results showed an increased risk for cancer development in the knockout mice. Growth retardation in new born mice has also been observed. In addition, no homozygous knockouts could be detected in these mice or their embryos indicating that gelsolin may involve embyogenesis or fertilization process in mice.

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