| Abstract: | 在台灣，肺癌高居癌症罹患率及死亡率中的第二位，治療方式主要以化學藥物治療為主，但肺癌細胞對於藥物所產生的抗藥性往往會阻礙化學治療的效果。過去文獻指出，中草藥萃取物對於多種癌症具有化學預防及治療的能力，因此本篇研究利用對抗癌藥docetaxel (DOC)具有抗藥性的A549/D16細胞株，探討一些中草藥萃取物是否可以直接或間接降低A549/D16的抗藥性現象。本研究選擇的九種中草藥包括欖仁葉、卷柏、紫丁地、夏枯草、補骨脂、骨碎補、葉下珠、穿山龍、風不動，經過乙醇萃取後的萃取物進行MTT assay結果顯示，這九種中草藥萃取物對A549及A549/D16細胞株的存活率均不會造成影響，表示這些中草藥萃取物皆不具細胞毒性。唯獨以補骨脂萃取物(Psorlaea corylifolia extract；PCE；100 μg/ml)合併抗癌藥DOC (16 nM)共同處理時，A549/D16細胞株的存活率可下降至70 %左右；以RT-PCR、real-time PCR和Western blot等方法進行分析後結果顯示，A549/D16細胞株中的ABCB1在基因層面及蛋白層面的表現量均有降低的趨勢。再以flow cytometry分析，確認ABCB1活性的確受到了補骨脂萃取物合併抗癌藥DOC處理的抑制。由以上實驗結果得知，補骨脂萃取物可能具有降低肺癌細胞的多重抗藥性以協助docetaxel毒殺癌細胞之能力。
In Taiwan, lung cancer has been the second leading cause for cancer incidence and mortality. With chemotherapy being the main treatment, multidrug resistance (MDR) of lung cancer cells to cytotoxic drugs significantly decreases the effectiveness of chemotherapeutic treatment. Previous studies have revealed that certain herbal extracts may exert potent activities for chemoprevention for various types of cancer. Therefore, the aim of this study was to investigate the capability of crude extracts from selected traditional chinese herbs on directly/auxiliary reversing the resistance of A549/D16 cells, which were drug-resistant sublines selected by docetaxel (DOC). These selected Chinese herbs include Terminalia catappa, Selaginella tamariscina, Syringa vulgaris, Prunella vulgaris, Psoralea corylifolia, Davallia mariesii Moore, Phyllanthus urinaria, Dioscorea nipponica Makino and Ficus pumila. As results shown, the cell viabilities of parental A549 or A549/D16 were not altered by any studied herbal extract, indicating the lack of cytotoxicity of these extracts. However, in a combination with DOC (16 nM), Psorlaea corylifolia L. extracts (PCE; 100 μg/ml) may reduce the cell viability of A549/D16 to about 70% by MTT assay. On the other hand, the ABCB1 gene and protein expression, an MDR-associated gene, was decreased in a dose-dependent manner, as shown in RT-PCR, real-time PCR experiments and western blotting. .Furthermore, the ABCB1 activity is inhibited by PCE, as detected by flow cytometry. These results revealed that PCE may be beneficial for the clinical management of lung cancer patients with MDR, which could be through an augment of cytotoxicity of DOC or a reverse of the MDR activity. |
