靈芝抗腫瘤效應之研究

Antitumor Effects of Ganoderma Lucidum

靈芝[Canoderma lucidum (Leyss. ex Fr.)Karst.]屬於真菌擔子(basidiomycotina)綱，其子實體之萃取物，顯示對ICR小鼠之惡性腫瘤(Sarcoma 180 tumor)具有抑制生長的作用。本實驗室亦發現，靈芝菌絲體(mycelium)之萃取物(GLP)，對公及母C3H小鼠之肌纖維惡性腫瘤(fibrosacaroma)具有抗腫瘤效果，而且對此惡性腫瘤細胞肺部遠隔轉移之病灶也具有抑制作用。以四倍體積的95%酒精來處理，可將GLP分成酒精沉澱物－GLP(AI)與酒精可溶物－GLP(AS)二部分，發現GLP(AI)是體內試驗中，對C3H小鼠之肌纖維惡性腫瘤產生抗腫瘤作用之主要成分。在靈芝抗腫瘤效應機轉的實驗中發現GLP(AI)可以增加抗體、誘導干擾素、增加自然殺手細胞，自然而然的增強宿主的免疫功能，抑制不正常的腫瘤細胞。最近實驗結果更發現靈芝能激發人類巨噬細胞產生細胞激素如腫瘤壞死因子(TNF-α)，間白細胞素(IL-1β)與造血因子(GM-CSF)，方各誘導人血癌細胞(Leukemic U937)分化效應的實驗中發現靈芝能刺激人血液單核細胞(Blood Mononuclear Cell)分泌細胞激素如INF-α、IFN-γ、IL-1β召等明顯的抑制人血癌細胞(U937)分裂(Proliferation)並誘導其分化(differentiation)完全。而於靈芝抗肺癌實驗時發現靈芝能有效延長肺癌動物存活時問與增加存活率。若與抗癌藥adriamycin、fluorouracil、thioguanine、methotrexate、cisplatin或人工合成免疫功能增強劑imexon合併使用更能有效的延長動物存活時間達三倍於控制組並顯著地降低動物死亡率。因此靈芝有明顯增進抗腫瘤免疫功能對腫瘤防治具有重要意義。

Ganoderma lucidum has been established to be an autitumor natural product. The hot water extracts of the mycelium of G. lucidum (GLP) exhibited antitumor effect against fibrosarcoma in male and female C3H mice and inhibited the metastasis of the tumor to the lung. Moreover, we have fractionated GLP into polysaccharide fraction [GLP(AI)] and non-polysaccharide fraction. We found that GLP (AI) is the major component to show the in vivo antitumor died on fibrosarcoma growth in C3H mice. The effects of GLP (AI) on cytotoxic activity of splenic natural killer cells (NK) were assessed in normal mice and in tumor hearing mice. The rsu1ts show that either intravenous, intraperitoneal or oral administration of GLP (AI) produced a dose-related increase in the splenic NK activity in different mouse strains. In addition, administration of GLP (AI) produced an increase in the titer of serum intertron (IFN). Furthermore, the decreased splenic NK cytotoxicity of tumor-hearing mice was restored by GLP (AI) treatment. The effect of GLP (AI) on the induction of differentiation in leukemic U937 cells was also examined. We found that it could stimulate blood mononuclear cells to secrete cytokines which were both anti-proliferative and differentiation inductive to the leukemnic U937 cells. Furthermore, antitumor activity of G. lucidum on intraperitoneally implanted Lewis lung carcinoma in synergenic C57BL/6 mice was investigated. The results showed that GLP significantly increasd the life-span of tumor-implanted mice, when administered intraperitoneally alone or in combination with cytotoxic antitumor drugs (adriamycin, fluorouracil, thioguanine, methotrexate, cisplatin) or synthetic immunomodulator (imexon). The GLP was not cytotoxic to cultured cells and the antitumor activity was abolished by pretreatment of mice with cyclosporine. The active principle (s) was found to be present predominantly in the GLP (AI) fraction.