Lentinan enhances sensitivity of mouse colon 26 tumor to cis-diamminedichloroplatinum (II) and decreases glutathione transferase expression.
We investigated the influence of a combination of lentinan, a biological response modifier, and cis-diamminedichloroplatinum(II) (CDDP) on the growth and glutathione S-transferase (GST) content of colon 26 tumor to examine whether lentinan represses GST expression and enhances the therapeutic effects of CDDP. Female CDF1 mice inoculated subcutaneously with transplantable colon 26 adenocarcinoma cells (1 X 10(6)/mouse) received intraperitoneal administrations of lentinan, CDDP, or the two drugs in combination, on days 10, 14, 17 and 21 after the inoculation. On day 24, tumor weights (estimated from their length and width) were significantly lower in the CDDP+ lentinan group (2.7+/-1.3 g) than in the CDDP alone group (4.3+/-0.7 g, P<0.05), both values being less than in the nontreated control group (7.2+/-1.5 g). The major GST form of colon 26 tumor was identified as GST-II, the Pi class form, and a minor form as GST-III belonging to the Mu class. Both GST-II and GST-III values on day 24 were significantly decreased in the lentinan alone (0.90+/-0.29 and 0.26 +/-0.11 microg/mg protein, respectively) and lentinan + CDDP groups (0.98+/-0.22 and 0.29+/-0.07 microg/mg protein), as compared with the control levels (1.39+/-0.20 and 0.52+/-0.11 microg/mg protein). However, these values were not different between the CDDP alone and lentinan + CDDP groups. Neither tissue interleukin (IL)-6, glutathione nor platinum values were different between the two groups. IL-6 values were elevated in about half of the samples treated with lentinan or CDDP and exhibited a modest inverse correlation with GST-II levels (r= -0.46). A GST inhibitor, ethacrynic acid, enhanced the sensitivity of cultured colon 26 cells to CDDP, suggesting the possible involvement of GST in modulating the cytotoxicity of CDDP to this cell line. These results indicated that lentinan administration decreases tissue GST-II and GST-III contents and enhances the sensitivity of colon 26 tumor to CDDP.
Murata
T
T
Second Department of Biochemistry, Hirosaki University School of Medicine, Zaifu-cho.
Hatayama
I
I
Kakizaki
I
I
Satoh
K
K
Sato
K
K
Tsuchida
S
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007155:Immunologic Factors / Q000008:administration & dosage; D007912:Lentinan / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D007912:Lentinan; D005982:Glutathione Transferase; D002945:Cisplatin