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 biologic al response modifier, and cis-diamminedichloroplatinum(II) (CDDP) on t he growth and glutathione S-transferase (GST) content of colon 26 tumo r to examine whether lentinan represses GST expression and enhances th e therapeutic effects of CDDP. Female CDS mice inoculated subcutaneous ly with transplantable colon 26 adenocarcinoma cells (1x10(6)/mouse) r eceived 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 tha n 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 min or form as GST-ZU belonging to the Mu class. Both GST-II and GST-III v alues on day 24 were significantly decreased in the lentinan alone (0. 90+/-0.29 and 0.26+/-0.11 mu g/mg protein, respectively) and lentinanCDDP groups (0.98+/-0.22 and 0.29+/-0.07 mu g/mg protein), as compared with the control levels (1.39+/-0.20 and 0.52+/-0.11 mu g/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 value s 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 o f 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 t o CDDP.