1930年代 Otto Heinrich Warburg提出瓦氏效應(Warburg effect)的假設，認為癌細胞可能是因為粒線體的缺陷，造成癌細胞在能量代謝上的轉換，由主要利用氧化磷酸化(oxidative phosphorylation)產生三磷酸腺苷(Adenosine triphosphate, ATP)轉變為利用糖解作用(glycolysis)來生成ATP，做為提供能量的來源。惡性腫瘤也是偏好利用糖解作用，過去發現很多惡性腫瘤有檸檬酸循環(Citric acid cycle)的酵素產生缺失。琥珀酸脫氫酶(Succinate dehydrogenase)有四個次單元，分別為A、B、C與D型，琥珀酸脫氫酶參與檸檬酸循環，並催化琥珀酸(succinate)轉變為延胡索酸(furmarate)，此外琥珀酸脫氫酶也參與電子傳遞鏈(electron transport chain)，做為電子傳遞鏈第二複合體來傳遞電子。琥珀酸脫氫酶乙型(Succinate dehydrogenase B)近年來的研究被認為是抑癌基因，在副神經節瘤與神經母細胞瘤的病人中，都可以發現琥珀酸脫氫酶乙型的突變。為了研究針對SDHB對肝癌惡性程度的影響，我挑選生長較慢的HepG2與HuH7細胞株做為建立穩定抑制SDHB的對象，在研究七株不同肝癌細胞的SDHB表現量，可以發現HepG2的SDHB表現量最高，而生長最快的SK-Hep1的SDHB表現量是最低。建立穩定抑制SDHB的HepG2與HuH7細胞株，分析他們生長、爬行以及細胞攤開能力，可以看見抑制SDHB會造成細胞生長、爬行以及細胞攤開能力上升，在分析SDH活性則會造成下降，而在酸鹼值的測定也比較偏酸性，抑制SDHB會造成細胞能量代謝偏向糖解作用並且造成細胞的惡性程度上升。我針對生長最快的SK-Hep1去過度表現SDHB，建立過度表現SDHB的SK-Hep1，去分析細胞生長、爬行以及攤開能力，可以看見過度表現SDHB會減緩細胞的生長、爬行以及攤開能力，分析SDH活性則會上升，而在酸鹼值的測定也比較偏鹼性，過度表現SDHB會增強檸檬酸循環並降低有氧糖解作用，進而降低肝癌細胞的惡性。本研究試圖去連接肝癌惡性程度與細胞內性SDHB的表現量高低，目前結果顯示出高表現量SDHB的肝癌細胞具有較低惡性程度，而低表現SDHB的肝癌細胞具有較高惡性程度，SDHB的表現扮演一個重要的角色影響著肝癌細胞的惡性程度。

In the 1930s, Otto Heinrich Warburg proposed the theory of Warburg effect. He thinks that mitochondria dysfunction would cause change in the cancer cells’ energy metabolism. When the normal cells transform into cancer cells, they would favorite to generate adenosine triphosphate (ATP) by glycolysis rather than oxidative phosphorylation. In research, many malignant tumors favorite glycolysis to generate energy and they also have enzyme dysfunctions in citric acid cycle. Succinate dehydrogenase is four subunits complex (SDHA, SDHB, SDHC, SDHD) and associates to citric acid cycle. The function of succinate dehydrogenase in citric acid cycle is that catalyzes the oxidation of succinate to furmarate. Succinate dehydrogenase also play a role in electron transport chain, serving as complex II to transfer the electron. In recently study, succinate dehydrogenase B is considered as a tumor suppressor, with the findings that the mutation of succinate dehydrogenase B in the patient of paraganglioma and pheochromocytoma. In order to study the tumor malignancy degrees of succinate dehydrogenase B in hepatocellular carcinoma, I choice HepG2 and HuH7 cell lines which are with low rate of tumor cell proliferation to be the stable knock down models. I analysis the endogenous SDHB protein expression in seven different hepatocellular carcinomas and HepG2 is the highest, but SK-Hep1 is the lower than the others. I figure out that knock down SDHB in HepG2 and HuH7 cell line increase the cell proliferation, cell migration and cell spreading. SDHB downregulation in HepG2 and HuH7 cell line decrease the SDH activity and cause the pH value of culture media to become acidic. It shifts the energy metabolism to use glycolysis and accelerates tumor malignancy that knock down SDHB protein expression. I establish a SDHB stable overexpression in SK-Hep1 cell line which is with high rate of tumor cell proliferation. SDHB overexpression in SK-Hep1 cell line arrests the cell proliferation, cell migration and cell spreading. SDHB overexpression in SK-Hep1 cell line increases the SDH activity and cause the pH value of culture media to become basic. SDHB overexpression increases the function of citric acid cycle and decreases glycolysis. This study establish the relationship between hepatocellular carcinoma tumor malignancy and endogenous SDHB protein expression level. The result presents that high SDHB protein expression level with low degree of tumor malignancy and low SDHB protein expression level with high degree of tumor malignancy in hepatocellular carcinoma. SDHB protein expression level plays the important role to affect the degree of tumor malignancy in hepatocellular carcinoma.

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