探討五種中藥單方處理非小細胞肺癌細胞株之效果

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2011

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替代性療法近來在許多疾病中因為療效良好而備受關注;其好處 為除了可以有效的治療疾病之外,相較之下,其所帶來的毒性或是副 作用可能低於傳統的治療方式。多年以來,肺癌即是許多國家癌症死 亡的首位,而本研究主要的目的就是想要探討傳統的中草藥配方是否 對於非小細胞肺癌細胞株A549, NCI-H460, NCI-H520 具有抑制其生 長或是存活的效果。我們對細胞分別用了五種不同的中草藥 (HC1-HC5)作處理,再探討這些藥物是透過甚麼樣的機制去減低細胞 生長的情形。我們發現在五種中草藥方內有兩種中草藥HC3以及HC4 對於減低非小細胞肺癌細胞株之存活率有顯著的影響,但相同的劑量 對於正常細胞株MRC5 則沒有太大的影響。另外我們也以流式細胞 儀以及西方墨點轉漬的實驗進一步的探討藥物處理對於細胞週期的 表現影響,我們發現在藥物處理後細胞族群較多停滯在G1 以及G2 的現象,分析調節細胞週期的蛋白質表現結果也符合流式細胞儀看到 的結果。除此之外,我們也發現了A549 側群細胞(具有類癌幹細胞的 特性)的比例在經過藥物處理後有顯著降低的趨勢,我們也分析了間 質-表皮轉換(MET)的相關蛋白以進一步的解釋癌幹細胞可能的變化 機制。另外我們也觀測到癌細胞的轉移能力因為藥物的處理而降低。 由我們的分析結果顯示這些藥物也許有潛力可以應用於肺癌治療。
Complementary Alternative Medicines (CAM) is attractive for its therapeutic efficacy, and its less toxic effect in some diseases than conventional treatments. Lung cancer has been the leading cause of cancer death in many countries since a few years ago. In this study we investigate if some of the Chinese Herbs have the therapeutic potential to suppress the proliferation or survival rate of Non-Small Cell Lung carcinoma (NSCLC) cell lines- A549, NCI-H460, and NCI-H520. We used five different herbal complexes (HC1-5) to treat the cells, and further investigated the mechanism that contribute to the reduction of cell survival rate. Two of the five complexes, HC3 and HC4, reduced the viability of cancer cells but not normal cells under the half maximal inhibitory concentration (IC50) dosage. The results of flow cytometry analysis indicated that these two HCs induced cell cycle arrested at G1 and G2 phases. We also confirmed this result by western blot analysis showing that the expression levels of several cell-cycle regulators, CDK4/6, cyclin D3 and cyclin B1were reduced after HC3 and HC4 treatment. In addition, side population (SP, which represented stem-like cancer cells) was also reduced after the treatment. To further elucidate the molecular mechanism, we examined the mesenchymal to epithelial transition (MET) on cells after treatment. Furthermore, we also performed the transwell assay to elucidate the cell migration ability after treatment. The data showed that both of HCs decreased the migration capacity of A549. In conclusion, these HCs may have potential to be applied to theNSCLC therapy.

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非小細胞肺癌, 中草藥, 癌幹細胞, NSCLC, Chinese herbs, CSCs

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