在1920年代，Otto Heinrich Warburg發現腫瘤細胞即使是在氧氣充足可利用的狀況之下，仍然會提高糖解作用的效率，並且產生大量的乳酸，這樣的現象被稱為”瓦氏效應”(Warburg effect)。然而Otto Heinrich Warburg認為瓦式效應的產生可能是粒腺體功能產生缺陷所造成的。琥珀酸脫氫酶乙型(SDHB)為琥珀酸脫氫酶的次單元之一，它的突變會造成副神經節瘤以及嗜鉻細胞瘤的產生。在本研究中，我嘗試利用小片段核醣核酸干擾技術抑制HeLa細胞中的琥珀酸脫氫酶乙型表現。在HeLa細胞成功建立了穩定抑制SDHB表現之細胞株後，觀察細胞之外型、細胞生長速度以及細胞爬行的速度皆與野生型之HeLa細胞株無差異。分析糖解作用與檸檬酸循環相關的蛋白質表現，發現在穩定抑制SDHB表現後，HK2之表現量有下降的現象。此外也分析了穩定抑制SDHB後，細胞內的能量代謝情形。 穩定抑制SDHB表現後造成細胞攝取葡萄糖能力上升，葡萄糖轉運體(glucose transporter 1 and 3)表現量上升，並且導致細胞內ATP含量下降，這可能代表細胞內的能量代謝偏向於糖解作用途徑。在處理不同葡萄糖濃度(0,1,4.5 mg/ml)或是在處理2-去氧葡萄糖(2-deoxyl glucose, 2-DG)的狀況之下，HeLa-shSDHB的細胞株顯示出比野生型細胞株具有更高的敏感性且細胞凋亡(apoptosis)之情形也更為明顯。另外在七株不同的肝癌細胞株(HepG2、Huh7、Hep3B、HepJ2、HepJ5、Mahlavu、SK-Hep1)當中發現，SDHB的表現量各不相同，以HepG2表現量最高，Mahlavu及SK-Hep1表現量最低。然而HepG2對於低葡萄糖濃度以及2-DG的處理狀態下，細胞生長不受影響，Mahlavu及SK-Hep1對於低葡萄糖濃度以及2-DG的處理狀態下，細胞生長則受到顯著的影響，且是偏向於細胞凋亡的途徑而死亡。本研究試圖連結肝癌細胞內生性SDHB表現量高低與細胞對於2-去氧葡萄糖的敏感性兩者之間的關聯，而目前的結果似乎顯示出SDHB的表現量與細胞對於2-去氧葡萄糖的敏感性兩者呈現反比的關係。

In the 1920s, Otto Warburg demonstrated that ascites tumor cells had high rates of glucose consumption and lactate production despite availability of sufficient oxygen to oxidize glucose completely, the phenomenon is called〝Warburg effect〞. However, Otto Warburg considered that Warburg effect may result from the dysfunction of mitochondria. Succinate dehydrogenase B (SDHB) is one of succinate dehydrogenase (SDH) subunits. Moreover, the mutation of SDHB is considered to cause paraganglioma and pheochromocytoma. In this study, I use RNAi technique to knockdown SDHB expression in HeLa cell, and I established a SDHB stable knockdown cell line successfully. After that, I analyzed glycolysis and TCA cycle-related protein expression, the hexokinase 2 (HK2) expression level is down-regulate. Interestingly, after treat with different glucose concentrations (0,1,4.5 mg/ml) or 2-deoxyglucose (2-DG) (0, 4, 10, 20mM), the SDHB deficient cell line appear to be more sensitive in low and no glucose condition or in 2-DG existence condition than wild type cell line. Furthermore, I discovered that SDHB expression level in seven different hepatoma cell lines is different in one another. SDHB expression of HepG2 is the highest, but Mahlavu and SK-Hep1 are lower than others. HepG2 is not sensitive to low glucose condition and 2-DG treatment, but Mahlavu and SK-Hep1 are sensitive to low glucose condition and 2-DG treatment. Moreover, Mahlavu and SK-Hep1 are toward to apoptosis pathway. This study try to establish the relationship between SDHB expression level and the sensitivity of cancer cells to glycolysis inhibition. So far, these data indicate that the relationship between SDHB expression level and the sensitivity of cancer cells to glycolysis inhibition maybe an inverse proportion.

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