| Objective: The experiment objective is to study the influence of thalidomide on cancer cachexia by establishing an experimental cancer cachectic model, observe the the influence on animation (water, food intake, body weight), biochemical indicators (total protein, triglyceride, cholesterol), serum cytokine (TNF-α) and nuclear transcription factor (AP-1), tumor angiogenesis (MVD) through prophylactic and normal using this drug and further to study the anti-cancer cachexia effect and the possible mechanism.Methods: A asuspension murine colonic adenocarcinoma cells(colon26)was inoculated into BALB / c mice on right armpit subcutaneously to build experimental cancer cachexia animal model. 82 male BALB/C mice were randomly divided into 5 groups: healthy control group (HC): ten mice, cancer cachexia with normal saline group(CC): eighteen mice, cancer cachexia with Medroxyprogesterone group(MPA): eighteen mice, cancer cachexia with prophylactic group(PLD): eighteen mice, cancer cachexia with thalidomide group(TLD): eighteen mice. Before the trial started, all mice in each group in the rearing cage one week to adapt to the new experimental environment. PLD group began to theraping with thalidomide from tumor-bearing mice subcutaneous tumor can be touched. Since the other tumor-bearing mice getting into cancer cachexia, CC group, MPA group, TLD group began to theraping with normal saline,thalidomide and Medroxyprogesterone for one week. Observations were made on the change of mice spirit, active, body weight, food and drink et al. Each group were sacrificed 10 mice after one week, the remaining eight in each group, respectively, continue the original treatment (dosage, frequency of medication unchanged) to its natural death. Application of omni-automatic biochemistry analyzer to measure the serum of the biochemical metabolic indicators; using radio immunoassay determination of plasma levels of TNF-α; using immunohistochemical methods in tumor tissue AP-1, MVD activity. Two independent grup means were compared using t test, multitude simple means were compared by One-Way analysis of variance (One-Way ANOVA).Results:1 Animal modelThree to five days later, the tumor could be touched on the tumor bearing mice after colone26 cells inoculated into each mouse. There were no significant changes in general condition, such as spirit and active stage et al. About two weeks later, the tumor bearing mice became thin, skin and fur became coarse, dark and gloomy. Their activities were slower than before and the sprit became worse. Drinking and eating reduced obviously. All the mice were in condition of cancer cachexia. With the medication in each group, the situations of the tumor bearing mice were improved in varying degrees.2 Tumor weight and Terminal non-tumor weightWith tumor size increasing, the non-tumor weight of all the tumor bearing mice decreased gradually after inoculated tumor cell. On the fifteenth day, the mean non-tumor weight in the tumor bearing mice became lower than that in healthy mice (P<0.05), all the mice were in condition of cancer cachexia. The tumor weight of medication group was lighten than that of CC, but there was on significant difference among all the tumor bearing groups. The removed tumor weight of PLD and MPA was higher than that of CC, and have significant difference (P<0.05).3 Biochemical indicatorsThe blood glucose and triglyceride levels appeared different degree of metabolic exhaustion in all tumor-bearing mice, and it had statistical significance (P<0.05). The serum level of total protein in all tumor-bearing mice was not obvious lower than that in CC group (P>0.05). The blood glucose of PLD was significant higher than that of CC (P<0.05), but it had no significant difference with that of MPA. The serum level of triglyceride in PLD was higher than that of CC,MPA , and had statistical significance (P <0.05).4 Serum cytokinesThe serum levels of TNF-αin tumor-bearing mice was obviously higher than that in HC (P<0.05). The serum levels of TNF-αin each group after treatment was significant lower than that in CC (P<0.05). The serum levels of TNF-αin PLD and TLD was lower than that in MPA (P<0.05), and The serum levels of TNF-αin PLD was lower than that in TLD, but the difference had not statistically significant (P>0.05).5 The expression of AP-1, MVD in tumor tissuesThe trend of the expression of MVD in tumor tissues is same to AP-1. The expression of AP-1, MVD in HC was significant lower than that in CC, the difference has a statistic significance (P<0.05), there was also statistic significance between CC and medication group (P>0.05). The expression of MVD in MPA and TLD was lower than that in CC, but this difference has no statistic significance (P>0.05).6 Span lifeThe mean span life in CC was longer than that in MPA,PLD,TLD,have significant difference (P<0.05). However, the mean span life of the three medication groups showed no statistical significance.Conclusions:1 The mice of cancer cachexia became thin, skin and fur became coarse, dark and gloomy. Their activities were slower than before, the sprit became worse, drinking and eating reduced, and their nutritional indexs obviously changed also. This experimental animal model was very similar to human cancer cachexia. It provides an ideal platform to further study on the happen and prevention and cure of cancer cachexia. 2 Besides the general state of decline, nutrition exhaustion, the serum cytokine TNF-αactivity in the mice of cancer cachexia also significantly increased. It suggests that metabolic disorder of saccharin, lipoids and protein showing in the mice of cancer cachexia may be associated with increased activity of proinflammatory cytokine.3 Thalidomide can improve the general situation of cancer cachexia mice, regulate of metabolic disorders, increase terminal non-tumor weight, and thus play an anti-cancer cachexia role. Thalidomide also superior to medroxyprogesterone in the aspect of down-regulating the expression of AP-1,MVD in tumor tissue and degrading serum level of TNF-α. In particular, the roles of thalidomide are even more evident when it was prophylacticd, and it suggested that early clinical intervention for the prevention and treatment of malignant tumor and the occurrence of cancer cachexia development had great significance.4 Medroxyprogesterone can increase the terminal non-tumor weight. This role of Medroxyprogesterone is superior to prophylactic thalidomide. In the lower AP-1, MVD in tumor tissues of the content, reduce serum TNF-αlevel, the were not significantly thalidomide. But it has no obvious effect on down-regulating the expression of AP-1,MVD in tumor tissue, degrading serum level of TNF-αand extensing of span life.
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