Yoshikawa Reigetsu, Yanagi Hidenori, Hashimoto-Tamaoki Tomoko, Morinaga Tomonori, Nakano Yoshiro, Noda Masafumi, Fujiwara Yoshinori, Okamura Haruki, Yamamura Takehira
Second Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Oncol Rep. 2004 Dec;12(6):1287-93.
Distant metastasis is one of the major problems in treatment for advanced colorectal cancer. Polysaccharide-K (PSK), or Krestin, a mushroom ingredient, has been used as a chemoimmunotherapeutic agent for the treatment of cancers in Asia for over 30 years. Some studies have reported that PSK prevent distant metastases and improve survival rates by 10-20% in colorectal cancer. However, the mechanism of the interrelated immunomodulatory and direct anti-cancer cell activities of PSK has yet to be elucidated. To investigate the direct effect, we used cDNA microarrays to analyse expression profiles in a human colorectal adenocarcinoma cell line, HCT116, containing the wild-type p53 gene. Expression of 453 genes was significantly altered (142 up-regulated and 311 down-regulated) after 96 h exposure to 500 microg/ml PSK. Under more stringent conditions, 9 genes were up-regulated and 36 down-regulated. We then examined the expression of candidate genes in two cell lines, HCT116, and SW480, a cell line with a mutant p53 gene. Our results suggest that PSK may augment anti-tumour action via genes including multidrug resistance protein 3 (MRP3), lymphotactin (Lptn), transgelin (TAGLN), and Pirin, without disturbing cell-cycle progression, and may deserve a large clinical trial in cancer therapy.
远处转移是晚期结直肠癌治疗中的主要问题之一。多糖-K（PSK），即云芝多糖，一种蘑菇成分，在亚洲作为癌症化疗免疫治疗药物已使用超过30年。一些研究报告称，PSK可预防远处转移，并使结直肠癌的生存率提高10%-20%。然而，PSK相关的免疫调节和直接抗癌细胞活性的机制尚未阐明。为了研究其直接作用，我们使用cDNA微阵列分析了含有野生型p53基因的人结肠腺癌细胞系HCT116的表达谱。在暴露于500μg/ml PSK 96小时后，453个基因的表达发生了显著变化（142个上调，311个下调）。在更严格的条件下，9个基因上调，36个基因下调。然后我们检测了候选基因在两种细胞系HCT116和具有突变型p53基因的细胞系SW480中的表达。我们的结果表明，PSK可能通过多药耐药蛋白3（MRP3）、淋巴细胞趋化因子（Lptn）、原肌球蛋白（TAGLN）和pirin等基因增强抗肿瘤作用，而不干扰细胞周期进程，并且可能值得在癌症治疗中进行大规模临床试验。
