Reevesioside A抑制人類肺癌細胞的機制探討

Exploring the anticancer mechanisms of reevesioside A in human lung cancer cells

林怡萱(Yi-Hsuan Lin)

指導教授 ： 王惠君

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2014年)

摘要

肺癌不論在男性或女性皆會造成高死亡率，其中有將近85-90%的患者屬於非小細胞肺癌。由於傳統的化學療法對於惡性肺癌效果不佳，因此，現在臨床上，改善化學療法已成為很重要的目標。在肺癌中STAT3的持續活化已被證實，因而在治療肺癌的發展上STAT3成為了一個重要的分子標的。
Reevesioside A屬於強心配糖體，從台灣梭羅木Reevesia formosana Sprague (Sterculiaceae) 根部所萃取出。我們利用細胞生長曲線觀察肺癌細胞對於reevesioside A的敏感性，並且以西方點墨法進行蛋白表現的分析。
結果中發現reevesioside A在nanomolar濃度範圍中即可抑制50%的肺癌細胞生長，且對於肺癌細胞較正常細胞有選擇性。西方點墨法分析結果顯示reevesioside A明顯抑制STAT3以及活化caspases的裂解，隨著劑量的增加效果更為顯著。AKT磷酸化在reevesioside A的作用下，視加藥時間的不同有不同的影響，我們發現AKT磷酸化在短時間會活化，長時間則減少。
在本研究中發現reevesioside A作用在肺癌細胞，是藉由抑制STAT3活化而產生抗癌活性，細胞因子及生長因子刺激下STAT3活化，我們將進一步探討STAT3在reevesioside A 作用下的機轉。

關鍵字

Reevesioside A ； 台灣梭羅木 ； 肺癌

並列摘要

Purpose Lung cancer is the leading cause of cancer deaths in both men and women. Approximately 85-90% of all cases of lung cancer are non-small-cell lung cancer (NSCLC). Malignancy in lungs cannot be effectively treated with the conventional chemotherapy. Therefore, improvement the chemotherapeutic effects are important in clinical treatment of lung cancer. Constitutively activated signal transducers and activators of STAT3 are frequently found in lung cancers. Thus, Stat3 can be an attractive molecular target for the development of cancer therapeutics.
Materials & Methods Reevesioside A, a cytotoxic cardenolide, isolated from the root of an endemic plant, Reevesia formosana Sprague (Sterculiaceae). We used cell growth curve to observe cell sensitivity to reevesioside A. Western blotting analysis were used to protein expression.
Results The cytotoxic IC50 value for revesioside A lies in the nanomolar concentrations in tested lung cancer cells. Treatment with reevesioside A in lung cancer cells at low dose (20 nM) resulted in decrease cell proliferation. Western blot data representing protein expression indicated that reevesioside A decreases STAT3 phosphorylation and activates caspase cascadein a dose-dependent manner. And we also found that AKT phosphorylation was increased in short time (2-4 hr) and decreased in long time (72 hr) of chemical ingredient exposure.
Conclusion This study discovers reevesioside A is a potent compound in treating lung cancers at least through inhibiting STAT3 activation. STAT3 can be activated by cytokines and growth factors mediated receptors, further investigation for the mechanism of reevesioside A on STAT3 activation is required for target gene identification.

並列關鍵字

Reevesioside A ； lung cancer

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