Phloretin誘發人類肝癌細胞株(HepG2)細胞凋亡之分子機制研究

Studies on the Molecular Mechanisms of Phloretin-induced Apoptosis in Hepatocellular carcinoma , HepG2 cell lines

蔡家怡(Chia-Yi Tsai)

指導教授 ： 何元順 博士

臺北醫學大學/醫學院/醫學檢驗生物技術學研究所/碩士(2004年)

摘要

肝細胞癌是國人最常見的癌症之一。近年來肝癌的診斷雖有很大的進步，但肝癌的治療效果仍然不盡理想，病人預後通常不佳。因素雖多，缺少有效抗癌藥物是一大主因，因此抗癌藥物的研發，重要性不可言喻。Phloretin是一種可以從蘋果、洋梨中萃取出來的天然化合物，也屬於多酚類物質之ㄧ，有文獻指出，Phloretin可以抑制某些腫瘤細胞生長,但仍未有研究指出，Phloretin造成細胞死亡的明確機轉為何。本研究證實Phloretin可以誘使人類肝癌細胞株(HepG2)發生細胞凋亡，且造成細胞凋亡的分子機制，包含了死亡受器調控路徑、粒線體調控路徑、與caspase-independent調控路徑等，本研究也證實出，合併投予同屬於天然抗癌物質的Phloretin及Paclitaxel，可以加強誘發細胞凋亡的現象。由於Phloretin具有抑制glucose transmembrane transport的功能，可以競爭性的抑制葡萄糖運送進入細胞，誘發細胞凋亡發生，本實驗透過合併投予高濃度的葡萄糖，可以有效阻斷細胞凋亡的發生；以及合併投予同樣會抑制葡萄糖運送進入細胞的Cytochalasin B(inhibitor of glucose transmembrane transport)，可以明顯的增加細胞凋亡比率，透過這些觀察，更加支持本實驗的推測，Phloretin可以誘使人類肝癌細胞株(HepG2)發生細胞凋亡，主要是透過抑制葡萄糖運送進入細胞的機制。

關鍵字

根皮素 ； 細胞凋亡 ； 肝細胞癌 ； 紫杉醇

並列摘要

Hepatocelluar carcinoma (HCC) is one of the common cancers in Taiwan. Although there have been great progresses in the diagnoses of HCC, the treatment of HCC is still disappointing with poor prognoses of the patients. Among the many probable causes of this phenomenon is the lack of effective anticancer therapies. Thus, the design of effective anticancer therapies is an important goal in research. Phloretin is occurring in apple, pear, which is related to flavornoids. Phloretin is known to inhibit tumor cell growth in vitro and in vivo.However, the mechanicsm of tumor cell death induced by phloretin has not been reported. In this study, we found Phloretin could induce apoptosis in HepG2 cells. The molecular mechanism of Phloretin induce cell apoptosis involved in death recaptor, mitochondria and caspase-independent pathway. Combination treatment of Phloretin and paclitaxel significantly increased the effect of apoptosis. Because Phloretin was reported to be a competitive inhibitor of glucose transport into the cells. Therefore, if the inhibition of glucose transport into the HepG2 cell is the trigger of Phloretin induced-apoptosis, the number of apoptotic cells will be reduced by the addition of excess glucose into the medium. Actually,since the induction of hypoidploid cells was remarkably inhibited by 100 m M glucose.

並列關鍵字

Phloretin ； Apoptosis ； Hepatocellular carcinoma ； Paclitaxel

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