生物體皆須能量來進行代謝運作。然而粒線體的缺失、缺氧環境的產生、致癌基因的活化以及代謝路徑中的酵素功能異常，可能使代謝改變造成正常細胞轉變為腫瘤細胞；在「瓦氏效應」中更說明其能量來源可能由氧化磷酸化（oxidative phosphorylation）偏向於使用糖解作用（glycolysis）。利用實驗室已建立之子宮頸癌細胞HeLa穩定抑制六碳醣激酶I （hexokinase I）、穩定抑制檸檬酸合成酶（citrate synthase）與肝癌細胞Hep3B穩定抑制琥珀酸脫氫酶乙型（succinate dehydrogenase B）這幾株貫穿糖解作用、檸檬酸循環（citric acid cycle）與電子傳遞鏈（electron transport chain）而因酵素缺陷而具有上皮—間質細胞轉型作用（epithelial mesenchymal transition）的高度惡性細胞來找尋能抑制較惡性的腫瘤細胞生長的方法。我利用了天然物白藜蘆醇（resveratrol），已知化療藥物2–去氧葡萄糖（2-deoxyglucose）、依托泊甘（etoposide）和放射線（radiation）及葡萄糖（glucose）限制來處理細胞。發現在低濃度白藜蘆醇處理下，酵素缺失的惡性細胞相較於野生株展現較專一的致死現象，初步得知細胞死亡原因與程式性凋亡（apoptosis）有關，詳細情況尚不清楚。而在2–去氧葡萄糖、依托泊甘、和放射線及葡萄糖限制下的處理結果，則都是酵素缺失的惡性細胞耐受性較野生株高。同時將HeLa穩定抑制檸檬酸合成酶細胞注入免疫缺陷（NOD/SCID）老鼠皮下，接著在固定時間給予不同濃度白藜蘆醇，可以觀察到腫瘤大小也隨藥物濃度提高而縮小，甚至沒有長出，這個現象可能暗示白藜蘆醇能夠在生物活體內（in vivo）抑制腫瘤生長。

All living organisms need energy to work, and ATP has been recognized as the major energy transfer molecule for cell metabolism. ATP can be generated by the two ways either oxidative phosphorylation (OXPHOS) or glycolysis pathway; the latter is preferred by most cancer cells to produce energy and this phenomenon is now known as the Warburg effect. Previous studies have suggested that metabolic changes, such as mitochondrial defects, hypoxia microenvironment, oncogenic signals, and altered metabolic enzymes may lead to the formation of tumor cells. Previously, our lab has established HKI (hexokinase I), CS (citrate synthase) stable knockdown cell lines in HeLa cell (HeLa-shHKI, HeLa-shCS) and SDHB (succinate dehydrogenase B) in Hep3B cell (Hep3B-shSDHB). All these stable knockdown cell lines exhibited highly malignant phenotypes, because of its proliferation and migration increased, which are obvious due to conversion of cell metabolism and epithelial mesenchymal transition (EMT) occurrence. Next in order to expore any effect on these highly malignant cell lines, we treated these cell lines with resveratrol, 2-deoxyglucose (2-DG), etoposide, radiation, and glucose at different concentrations. As the result shown, only the natural product resevratrol can specificity inhibit the growth of highly malignant tumors at low dose by inducing apoptosis. Furthermore, the tumor xenograft model was established. When the HeLa-shCS cells were injected subcutaneous in NOD/SCID mice, we also found that significantly tumor growth was inhibited after resveratrol treatment. This study for the first time directly shows that antiproliferative and apoptotic effects of dietary compound resveratrol in highly malignant human cervical cancer can be induced by knockdown of respiratory enzyme CS expression in vitro and in vivo.

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