靈芝自古即被”神農本草經 ”與”本草綱目”列為上品中草藥，具有延年益壽功能。近年來亦有相關文獻報導靈芝具有抗老化與抗腫瘤效果。另外先前的研究指出腫瘤初始形成及免疫耐受性的產生與吲哚胺 2,3-雙氧化酶 (IDO) 蛋白有很大的相關性，IDO藉由催化必需胺基酸色胺酸而抑制了對色胺酸短缺極為敏感的T細胞增生，造成T細胞生長受到抑制。此外，第二型人類表皮生長因子受體 (HER2) 與癌症的惡性度息息相關，包括腫瘤的增生、轉移、侵襲能力，造成癌症臨床預後效果不佳的狀況。因此，本論文探討靈芝是否可藉由抑制HER2誘導產生的IDO進而抑制癌細胞的免疫逃脫現象。結果發現靈芝乙醇萃取物在HER2高度表現細胞株中具有濃度依賴性的抑制HER2的表現，此種抑制現象在RNA及蛋白質的層次上皆有相同的效果。HER2受抑制後，進而使IDO基因及其蛋白表現也受到抑制。綜合以上結果顯示靈芝乙醇萃取物具有抗癌效果，同時藉由抑制IDO的基因表現，顯示也可能具有增強免疫能力的作用，是一個極具有開發潛力的中草藥。
Lingzhi has been classified as one of the best grade of traditional Chinese medicines (TCMs) by the Chinese ancient medical encyclopedia, ”Shen-Nong-Ben-Cao-Jing” and “Ben-Cao-Gang-Mu”. Recent reports have shown that Lingzhi, including Ganoderma tsugae, has anti-tumor and antioxidative properties. On the other hand, the protein indoleamide 2,3-dioxygenase (IDO) has been demonstrated to be closely involved in tumor formation and immune tolerance. IDO catalyzes the metabolism of the essential amino acid “tryptophan” resulting in blocking T cell proliferation. While the aberrant expression of human epithelial growth factor receptor 2 (HER2; ErbB2) is known to be associated with cancer malignancy, including tumor progression, tumor metastasis, and invasive abilities, leading to poor clinical outcomes. In this study, we reveal that the Ganoderma tsugae ethanol extract (GTEE) can be used to down-regulate the expression of HER2 in HER2-overexpression cancer cell lines. Furthermore, the differential suppression of HER2 is in response to the inhibition of IDO along with a dose-dependent increase of GTEE. These results provide that GTEE may be a potential TCM for blocking tumor immune escape and enhancing anti-tumor effects.
