肺癌是造成全世界最具威脅的癌症之一。 最主要的原因之一是在化學治療後會產生化療抗藥性。牛樟菇(Antrodia cinnamomea, AC)為一中草藥，又名樟芝或牛樟菇，為台灣特有真菌種。 目前已知AC具可能的抗癌作用，但其對肺癌仍無相關研究證實。 我們的實驗目的是探討AC是否可對化療抗藥性肺腺癌細胞株具有可能的毒殺效益。 我們先以臺灣肺腺癌患者的腫瘤檢体建立本土型肺腺癌細胞株，再以2 μg/ml和5 μg/ml不同濃度的化療藥物：順鉑(cisplatin) 建立出具有順鉑抗藥性的肺腺癌細胞株為細胞模式。 分別利用MTT assay、Wound healing assay、Flow cytometry 及Western blot來檢測AC是否會抑制細胞生長效果、細胞遷移能力、調控細胞週期及細胞凋亡及Bax/Bcl-2的蛋白表現量。結果顯示，AC對於肺腺癌細胞株有明顯的劑量依賴性毒殺作用。對具有順鉑抗藥性的肺腺癌細胞株而言，AC可以再提高其毒殺作用。Wound healing assay結果顯示，當AC濃度在20 mg/ml時，對於具有順鉑抗藥性的肺腺癌細胞株有顯著抑制其細胞遷移能力。AC可部分抑制S+G2M期，同時也會增加細胞凋亡比例。細胞凋亡蛋白分子Bax表現量增加和Bcl-2降低，推測AC可能會啟動內原性途徑的凋亡。 我們認為AC可能可以增強毒殺順鉑抗藥性肺腺癌細胞株能力。
Lung cancer is one of the highest threaten cancers in the world. The most problem of the treatment is believed the chemodrug resistance. Antrodia cinnamomea (A. Cinnamomea; AC), a medicinal mushroom in Taiwan, has been shown anticancer activities. To investigate a novel anticancer effectiveness by pretreating patient-derived non-small cell lung cancer cells (NSCLCs) with cisplatin follwed by the administration of AC, the cisplatin-resistant patient derived NSCLCs were established with a 6-period of cisplatin treatments at 2 μg/ml and 5 μg/ml respectively. The capabilities of AC in cytotoxicity, migration, cell cycle, apoptosis and Bax/Bcl-2 proteins were evaluated respectively. Our results showed significant dose-dependent cytotoxicity in patients-derived NSCLCs. The nontoxic dose of AC enhanced the cytotoxicity of cisplatin-resistant patient-derived NSCLCs. The wound healing assay showed significant inhibitory effect in cisplatin-resistant NSCLCs when AC was treated at 20 mg/ml. Additionally, the enhanced apoptotic effect as characterized by increased Bax and decreased protein levels of Bcl-2 and S+G2M phase was reduced by AC treatment. Our results provide the first evidence that AC induced signigicant higher cytotoxicity and triggered intrinsic apoptosis in cisplatin-resistant NSCLCs.
