在癌症治疗的探索中，食用菌以其独特的生物活性成分开辟了新路径。作为天然的分子宝库，食用菌通过多靶点机制抑制肿瘤进展，并以免疫调节和耐药逆转的双重特性，为现代肿瘤治疗注入革新力量。一篇由嘉泉大学的Hye-Jin Park在《International Journal of Molecular Sciences》上发表了题为“Current Uses of Mushrooms in Cancer Treatment and Their Anticancer Mechanisms”的综述为大家讲述了食用菌在癌症治疗中的应用现状及其抗癌机制。

食用菌中蕴含的β-葡聚糖、三萜类及酚类化合物构成其抗癌核心。β-葡聚糖通过激活Toll样受体（TLR）诱导树突状细胞成熟，增加CD8+ T细胞浸润，显著增强肿瘤免疫监视功能^[1]。三萜类成分（如灵芝酸Ganoderic acid）通过抑制PI3K/AKT通路磷酸化，使肝癌细胞凋亡率增加65%，并协同顺铂将化疗敏感性提升40%^[2]。桑黄（Phellinus linteus）多糖通过下调Wnt/β-catenin通路关键蛋白cyclin D1，诱导结肠癌细胞周期阻滞于G0/G1期，同时抑制转移相关基因MMP-9的表达^[3]。这些成分的多靶点作用既可直接杀伤肿瘤细胞，又能重塑肿瘤微环境。

克服多药耐药性是食用菌成分的突出优势。鸡油菌（Cantharellus cibarius）提取物通过抑制P-糖蛋白（P-gp)外排功能，增加紫杉醇在耐药结肠癌细胞中的蓄积量，其逆转效果与维拉帕米相当^[4]。灵芝（Ganoderma lucidum）多糖肽能靶向PD-1/PD-L1轴，下调PD-1蛋白表达，在黑色素瘤模型中提升免疫检查点抑制剂的应答率[5]。更有研究发现，白桦茸（Inonotus obliquus）多糖通过阻断CTLA-4与CD80结合，提升了细胞毒性T细胞的活化效率^[6]。这种多靶点干预策略为破解耐药难题提供了新范式。

在信号通路调控层面，食用菌成分展现出精准的分子干预能力。蛹虫草素（Cordycepin）通过抑制NF-κB核转位，降低乳腺癌细胞IL-6分泌量，同时增强TNF-α诱导凋亡的敏感性^[7]。桑黄（Phellinus linteus）中的Hispolon通过抑制ERK/FAK通路，降低肝癌细胞侵袭能力^[8]。

临床研究数据为食用菌的转化潜力提供佐证。在III期非小细胞肺癌患者中，灵芝（Ganoderma lucidum）提取物提升了CD3+ T细胞和NK细胞活性，同时降低化疗相关疲劳的发生率^[9]。针对转移性肝癌的随机对照试验显示，云芝（Coriolus versicolor）多糖联合常规治疗延长了患者中位生存期，提高了疾病控制率^[10]。但部分研究也暴露局限性：香菇多糖单药治疗前列腺癌未显示显著疗效，提示联合用药方案需优化^[11]。

从实验室到临床，食用菌抗癌研究已跨越初步验证阶段，正向精准医疗迈进。其多组分、多靶点的特性既符合系统医学理念，也为个体化治疗提供丰富资源。随着作用机制的深度解析和制剂工艺的持续革新，这一古老生物正焕发新的治疗潜能。

参考文献：

[1]  Wasser, S.P. Medicinal Mushrooms in Human Clinical Studies. Part I. Anticancer, Oncoimmunological, and Immunomodulatory Activities: A Review. Int. J. Med. Mushrooms 2017, 19, 279–317.

[2]  Cheng, Y.; Xie, P. Ganoderic acid A holds promising cytotoxicity on human glioblastoma mediated by incurring apoptosis and autophagy and inactivating PI3K/AKT signaling pathway. J. Biochem. Mol. Toxicol. 2019, 33, e22392.

[3]  Song, K.S.; Li, G.; Kim, J.S.; Jing, K.; Kim, T.D.; Kim, J.P.; Seo, S.B.; Yoo, J.K.; Park, H.D.; Hwang, B.D.; et al. Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/β-catenin in SW480 human colon cancer cells. BMC Cancer 2011, 11, 307.

[4]  Choi, C.W.; Yoon, J.-W.; Yon, G.H.; Kim, Y.S.; Ryu, S.Y.; Seok, S.-J.; Kang, S.; Kim, Y.H. Multidrug resistance reversal activity of methanol extracts from basidiomycete mushrooms in cancer cells. Nat. Prod. Sci. 2012, 18, 239–243.

[5]  Wang, G.; Wang, L.; Zhou, J.; Xu, X. The Possible Role of PD-1 Protein in Ganoderma lucidum-Mediated Immunomodulation and Cancer Treatment. Integr. Cancer Ther. 2019, 18, 1534735419880275.

[6]  Kim, T.I.; Choi, J.-G.; Kim, J.H.; Li, W.; Chung, H.-S. Blocking Effect of Chaga Mushroom (Inonotus obliquus) Extract for Immune Checkpoint CTLA-4/CD80 Interaction. Appl. Sci. 2020, 10, 5774.

[7]  Kadomatsu, M.; Nakajima, S.; Kato, H.; Gu, L.; Chi, Y.; Yao, J.; Kitamura, M. Cordycepin as a sensitizer to tumour necrosis factor (TNF)-α-induced apoptosis through eukaryotic translation initiation factor 2α (eIF2α)- and mammalian target of rapamycin complex 1 (mTORC1)-mediated inhibition of nuclear factor (NF)-κB. Clin. Exp. Immunol. 2012, 168, 325–332.

[8]  Huang, G.J.; Yang, C.M.; Chang, Y.S.; Amagaya, S.; Wang, H.C.; Hou, W.C.; Huang, S.S.; Hu, M.L. Hispolon suppresses SK-Hep1 human hepatoma cell metastasis by inhibiting matrix metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt and ERK signaling pathways. J. Agric. Food Chem. 2010, 58, 9468–9475.

[9]  Gao, Y.; Dai, X.; Chen, G.; Ye, J.; Zhou, S. A randomized, placebo-controlled, multicenter study of Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetideae) polysaccharides (Ganopoly®) in patients with advanced lung cancer. Int. J. Med. Mushrooms. 2003, 5, 14.

[10]  Chay, W.Y.; Tham, C.K.; Toh, H.C.; Lim, H.Y.; Tan, C.K.; Lim, C.; Wang, W.W.; Choo, S.P. Coriolus versicolor (Yunzhi) Use as Therapy in Advanced Hepatocellular Carcinoma Patients with Poor Liver Function or Who Are Unfit for Standard Therapy. J. Altern. Complement. Med. 2017, 23, 648–652.

[11]  White, R.W.d.; Hackman, R.M.; Soares, S.E.; Beckett, L.A.; Sun, B. Effects of a mushroom mycelium extract on the treatment of prostate cancer. Urology 2002, 60, 640–644.

文献链接：https://pubmed.ncbi.nlm.nih.gov/36142412/