Gene expression in response to anti-tumour intervention by polysaccharide-K (PSK) in colorectal carcinoma cells.
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.
Yoshikawa
Reigetsu
R
Second Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. yosikr2s@hyo-med.ac.jp
Yanagi
Hidenori
H
Hashimoto-Tamaoki
Tomoko
T
Morinaga
Tomonori
T
Nakano
Yoshiro
Y
Noda
Masafumi
M
Fujiwara
Yoshinori
Y
Okamura
Haruki
H
Yamamura
Takehira
T
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011509:Proteoglycans / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D011509:Proteoglycans; D016159:Tumor Suppressor Protein p53; C010770:polysaccharide-K