樟芝子實體乙醇萃取物對原發性腫瘤微環境中與發炎相關生物指標之影響

Abstract

發炎反應在腫瘤發展的不同階段扮演著舉足輕重的角色，包含腫瘤形成、增殖、惡化、侵蝕與轉移。發炎性的環境對於腫瘤的進展具有深遠的影響。當改變腫瘤微環境中與發炎相關之因子之表現量時能調控腫瘤的生長。本研究利用乙醇萃取樟芝子實體，觀察以口服灌食和塗抹方式來探討給予擔癌小鼠樟芝萃取物後，血清及腫瘤微環境中與發炎相關細胞激素、生長因子以及原發性腫瘤生長之影響。 結果顯示，樟芝乙醇萃取物可降低小鼠肺癌細胞株(Lewis Lung Carcinoma)之活性，LLC活性的抑制有濃度依賴關係。口服灌食8 mg/kg 體重劑量樟芝萃取物可降低擔癌小鼠血清中COX-2及VEGF含量，並降低擔癌小鼠原發位腫瘤微環境中IL-1β、TNF-α、IL-6、COX-2、PTGER2與VEGF等發炎相關因子之基因表現量，並且減緩小鼠大腿原發位腫瘤的體積與重量生長。同時，口服樟芝乙醇萃取物搭配塗抹樟芝三萜類萃取物對原發性腫瘤的抑制、血清與腫瘤微環境中發炎相關因子與單純口服樟芝萃取物並未發現有顯著性的差異。 總括上述，樟芝萃取物降低了小鼠肺癌細胞株之活性、降低擔癌小鼠血清與腫瘤微環境中發炎相關因子的表現量，以及減緩原發性腫瘤的生長。未來在癌症治療應用方面，樟芝萃取物可能具有輔助性治療的潛力。

Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation in the tumor microenvironment induces many tumor-promoting effects. The present study is to investigate the effect of oral administration and skin smear of ethanol extract of fruit body of Antrodia cinnamomea (EEAC) on inflammation-related cytokines and growth factors in the primary tumor microenvironment. The results showed that EEAC treatment dose-dependently reduced LLC cell viability. For LLC tumor model, oral administration 8 mg/kg of body weight of EEAC significantly reduced COX-2 and VEGF production in serum. In addition, IL-1β、TNF-α、IL-6、COX-2、PTGER2 and VEGF mRNA expression were substantially declined within the tumor microenvironment after oral EEAC treatment, and the primary tumor was significantly suppressed. However, oral administration and skin smear of EEAC showed no significant variation neither in tumor growth nor inflammation-related factor expression in serum and the tumor microenvironment between the treated mice. To sum up, EEAC reduced LLC cell viability, COX-2 and VEGF production in serum, and inflammation-related mRNA expression declined within the tumor microenvironment. Results obtained from the present study may suggest that EEAC may possess a potentiality for cancer chemotherapeutic activity.