Thalidomide attenuates tumor growth and preserves fast-twitch skeletal muscle fibers in cholangiocarcinoma rats

BackgroundThe prognosis for cholangiocarcinoma remains dismal due to a low resection rate and early recurrence. Cancer cachexia is associated with decreased survival and poor quality of life. Herein, we present a rat model of cholangiocarcinoma and demonstrate that thalidomide attenuates tumor growth and improves cachexia.MethodsA cholangiocarcinoma model was established using Sprague-Dawley rats that were fed thioacetamide for 40 weeks. Cholangiocarcinoma rats were treated using either thalidomide or saline for 8 weeks. Tumor growth and body weight were recorded for all animals. The expression of CD31, VEGF, and eIF4E of cholangiocarcinoma were determined using immunohistochemistry. Level of apoptosis and Fas-mediated apoptosis genes of cholangiocarcinoma were determined using TUNEL assay and ribonuclease protection assay, respectively. The distribution of fast-twitch soleus skeletal muscle fibers was determined as was the expression of TNFα and TGFβ1 within soleus muscle.ResultsAfter an 8-week treatment, the mean weight of saline- and thalidomide-treated rats was 24% and 19%, respectively, less than that of control (ANOVA, P   < .05). The tumor volume (x¯±SD) of thalidomide-treated rats was less than saline-treated rats (1.9 ± 0.4 vs 4.6 ± 1.3 cm3, P < .01). The expression of CD31, eIF4E, and VEGF of cholangiocarcinoma was less than thalidomide-treated rats than for saline-treated rats, while the level of apoptosis of tumor cells was greater for thalidomide- treated rats than for saline-treated rats. The expression of mRNA for Fas, caspase-3, and Bax of cholangiocarcinoma in the thalidomide-treated rats was greater than for saline-treated rats. The number of fast-twitch skeletal muscle fibers per 500 mm2 of control, saline-, and thalidomide-treated rats was 43 ± 6, 14 ± 3, and 41 ± 8 (ANOVA, P < .001). The expression of TNFα and TGFβ1 of soleus muscles for thalidomide-treated rats was less than for saline-treated rats.ConclusionsUsing our rat cholangiocarcinoma model, we demonstrated that thalidomide inhibited tumor growth and was associated with a decrease in expression of reduced eIF4E and VEGF expression; in addition, thalidomide preserved fast-twitch skeletal muscle fibers and was associated with decreased expression of TNFα and TGFβ1.