Elucidation of pathophysiological significance of LIF and development of new treatment strategy in prostate cancer

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In vitro culture of JCA-1 cells produced a time dependent increase in medium levels of leukemia inhibitory factor (LIF). An NFkappaB inhibitor produced an inhibitory effect on LIF production in JCA cells. On the other hand, recombinant LIF demonstrated no significant effects on cell growth in prostate cancer cell lines, PC3, DU145 and JCA-1 cells. Serum levels of LIF in nude mice having JCA-1 tumors and PC3 tumors were increased, respectively, whereas those in control nude mice without tumors were not detected. At the same time, JCA-1 tumor-bearing mice produced a decrease in body weight 28 days after inoculation, although mice without tumors showed an increase in body weight. In vitro culture of JCA-1 cells also produces IL-6. Serum levels of IL-6 were also significantly elevated in JCA-1 tumor bearing nude mice accompanied with a loss of body weight when compared with control mice without tumors. Then, serum levels of LIF and IL-6 were measured in patients with prostate cancer. Serum … More levels of LIF were not detected in a majority of untreated patients and patients with progression after endocrine therapy. On the other hand, serum IL-6 levels were significantly elevated in untreated patients with stage D disease when compared with stage A, B and C patients. Serum IL-6 levels further increased in patients with progression after endocrine therapy. The serum total protein and albumin levels, hemoglobin levels, and body mass index of the patients with higher serum IL-6 levels were significantly lower than the corresponding values in patients with lower serum IL-6 levels. Significant correlation between serum IL-6 and serum albumin levels, hemoglobin levels, body mass index and performance status was found. An NFkappaB inhibitor produced statistically significant increase in body weight, epididymal fat and gastrocnemius muscle weight in JCA-1 tumor bearing nude mice, when compared to control mice. Hematocrit, serum albumin and triglyceride levels were significantly higher and serum IL-6 levels were significantly lower in treated mice than control mice. These results suggest that serum IL-6 may be associated with cachexia and an NFkappaB inhibitor may prevent the development of cancer cachexia induced by prostate cancer through the suppression of IL-6 in an animal model. Less