Habelhah H, Okada F, Nakai K, Choi S K, Hamada J, Kobayashi M, Hosokawa M
Laboratory of Pathology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan.
Cancer Immunol Immunother. 1998 Aug;46(6):338-44. doi: 10.1007/s002620050495.
Previously we reported the malignant progression of QR-32, a regressor-type tumor clone, following co-implantation with foreign bodies (gelatin sponge or plastic plate) in normal syngeneic C57BL/6 mice. We also reported that the progression of QR-32 cells by a gelatin sponge was significantly inhibited in the mice administered polysaccharide K (PSK) and that PSK induced an increase of radical scavengers, especially manganese superoxide dismutase (Mn-SOD), locally at the site of tumor tissues. In this study, to reveal the possible mechanism by which PSK induced Mn-SOD in the tumor tissues, we examined the mRNA expression and protein levels of inflammatory cytokines in the tissues. We found that mRNAs of tumor necrosis factor alpha (TNFalpha) and interleukin-1alpha (IL-1alpha) were considerably expressed in both PSK-treated and phosphate-buffered-saline-treated tumors, and that the mRNA expression and protein level of interferon gamma (IFNgamma) increased in the tumor tissues treated with PSK. In vitro treatment of QR-32 cells with IFNgamma did not significantly increase the production of Mn-SOD; however, the combination of IFNgamma with TNFalpha increased the Mn-SOD production more effectively than did any of the cytokines used singly. Furthermore, we observed the down-regulation of the mRNA expression and protein level of transforming growth factor beta (TGFbeta) in the tumor tissues treated with PSK, and that in vitro treatment of QR-32 cells with TGFbeta decreased the production of Mn-SOD. These results suggest that PSK suppresses the progression of QR-32 cells by increasing Mn-SOD via the modulation of inflammatory cytokines; that is, by decreasing TGF-beta and increasing IFN-gamma.
此前我们报道过，在正常同基因C57BL/6小鼠体内，将消退型肿瘤克隆QR-32与异物（明胶海绵或塑料板）共同植入后，QR-32会发生恶性进展。我们还报道过，在给予多糖K（PSK）的小鼠中，明胶海绵介导的QR-32细胞进展受到显著抑制，并且PSK可诱导肿瘤组织局部自由基清除剂增加，尤其是锰超氧化物歧化酶（Mn-SOD）。在本研究中，为揭示PSK在肿瘤组织中诱导Mn-SOD的可能机制，我们检测了组织中炎性细胞因子的mRNA表达和蛋白水平。我们发现，肿瘤坏死因子α（TNFα）和白细胞介素-1α（IL-1α）的mRNA在PSK处理组和磷酸盐缓冲盐水处理组的肿瘤中均有大量表达，并且在PSK处理的肿瘤组织中，干扰素γ（IFNγ）的mRNA表达和蛋白水平升高。用IFNγ体外处理QR-32细胞并未显著增加Mn-SOD的产生；然而，IFNγ与TNFα联合使用比单独使用任何一种细胞因子更有效地增加了Mn-SOD的产生。此外，我们观察到在PSK处理的肿瘤组织中，转化生长因子β（TGFβ）的mRNA表达和蛋白水平下调，并且用TGFβ体外处理QR-32细胞会降低Mn-SOD的产生。这些结果表明，PSK通过调节炎性细胞因子增加Mn-SOD来抑制QR-32细胞的进展；也就是说，通过降低TGF-β并增加IFN-γ来实现。
