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

体外培养的JCA-1细胞产生了白血病抑制因子（LIF）中水平的时间依赖性增加。NFkappaB抑制剂对JCA细胞的LIF产生抑制作用。另一方面，重组LIF对前列腺癌细胞系、PC3、DU145和JCA-1细胞的生长无显著影响。JCA-1肿瘤裸鼠和PC3肿瘤裸鼠血清LIF水平分别升高，而对照组裸鼠未检测到LIF水平。同时，JCA-1荷瘤小鼠在接种后28天体重下降，而无肿瘤小鼠体重增加。体外培养的JCA-1细胞也产生IL-6。与未患肿瘤的对照组小鼠相比，JCA-1荷瘤裸鼠血清IL-6水平也显著升高，并伴有体重减轻。然后，测量前列腺癌患者血清中LIF和IL-6的水平。在大多数未经治疗的患者和内分泌治疗后进展的患者中未检测到更多水平的LIF。另一方面，与A、B、C期患者相比，未经治疗的D期患者血清IL-6水平显著升高。患者在内分泌治疗后血清IL-6水平进一步升高。血清IL-6水平较高的患者血清总蛋白和白蛋白水平、血红蛋白水平和体重指数均显著低于血清IL-6水平较低的患者。血清白细胞介素-6与血清白蛋白水平、血红蛋白水平、体重指数及生产性能状况存在显著相关。与对照组小鼠相比，NFkappaB抑制剂使JCA-1荷瘤裸鼠体重、附睾脂肪和腓肠肌重量有统计学意义的增加。治疗组小鼠红细胞压积、血清白蛋白和甘油三酯水平显著高于对照组小鼠，血清IL-6水平显著低于对照组小鼠。这些结果表明，血清IL-6可能与恶病质有关，NFkappaB抑制剂可能通过抑制IL-6在动物模型中阻止前列腺癌诱导的癌症恶病质的发展。少

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