| During the 2008, an estimated 34290 people will die of pancreatic adenocarcinoma, which is the fourth leading cause of cancer death in the United States. However, the incidence appears to have increased steadily in china in recent years. At the time of diagnosis, 80% of patients present with either locally advanced or metastatic disease. In recent years, although gene therapy and biological targeting therapy have demonstrated the significant growth inhibition of pancreatic cancer in animal experiment, there is no satisfactory therapeutic method for pancreatic cancer patients to extend median survival and total survival rate. The overall five-year survival rate is still less than 5%.The stress associated with the diagnosis and treatment of pancreatic cancer can cause significant psychiatric morbidity. It has been reported that pancreatic cancer patients are associated with the highest rate of major depression in comparison with other cancers. Depression has been demonstrated in 47%-71% of patients with pancreatic cancer. Depression adversely affects many clinical oncology outcomes, such as prolongs the length of hospital stay, augments the complication with therapy, decreases ability to care for society, reduces compliance with medical treatment and poorer quality of life, perhaps even shortens survival time. Antidepressant medications not only improve depressive symptoms in patients with cancer but also positively reverse these adverse impacts.Clearly, antidepressant treatment had constituted one of the new strategies of cancer adjuvant therapy. However, data on treatment of depression with antidepressant in cancer patients were relatively scarce. The effectiveness of different agents on distressing symptoms of cancer patients were still subject for discussion. Brandes reported stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses. Therefore , to evaluate the safe and efficacy of antidepressants on pancreatic cancer, our present study was divided into three parts:1,Experimental study of antidepressants in a pancreatic cancer xenograft mouse model: to investigate the effects of mirtazapine and fluoxetine, served as representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and selective serotonin reuptake inhibitors (SSRIs) antidepressant respectively, on ingestive behavior, body weight, tumor growth of human pancreatic carcinoma xenografts and locomotor activity in nude mice.2,Adjunctive effects of mirtazapine in a pancreatic cancer model treated with gemcitabine chemotherapy: observe the effects of mirtazapine in combination with gemcitabine on food intake, body weight and tumor growth of human pancreatic carcinoma xenografts in nude mice. To evaluate whether mirtazapine reverses these adverse effects of chemotherapy.3,Adjunctive effects of mirtazapine in a pancreatic cancer model treated with photodynamic therapy: to evaluate the safe and efficacy of mirtazapine in combination with photodynamic therapy on a mouse model of pancreatic carcinoma xenografts.Methods1,Experimental study of antidepressants in a pancreatic cancer xenograft mouse model: a subcutaneous xenograft mouse model of human pancreatic cancer SW1990 was established. The tumor-bearing mice were randomly divided into saline solution control group, mirtazapine group, fluoxetine group, with 7 mice in each group. All mice were treated once daily with saline solution, mirtazapine (10mg/kg), fluoxetine (10mg/kg), orally by using metal gavage feeding needles for 42 days. Food intake, body weight, tumor size and locomotor activity were investigated.2,Adjunctive effects of mirtazapine in a pancreatic cancer model treated with gemcitabine chemotherapy: a subcutaneous xenograft mouse model of human pancreatic cancer was established. The tumor-bearing mice were randomly divided into control group, gemcitabine group, mirtazapine plus gemcitabine group, with 8 mice in each group. All mice received once daily with an equivalent normal saline solution, saline solution and mirtazapine (10mg/kg) respectively, orally by using metal gavage feeding needles for 21 days. Gemcitabine group and mirtazapine plus gemcitabine group received intraperitoneal injections of gemcitabine (100 mg/kg per dose) on days 1, 4, 7and 10 after establishing a subcutaneous xenograft mouse model. Food intake, body weight and tumor size were compared among three groups.3,Adjunctive effects of mirtazapine in a pancreatic cancer model treated with photodynamic therapy: a subcutaneous xenograft mouse model of human pancreatic cancer was established. The tumor-bearing mice were randomly divided into control group, photodynamic therapy group, mirtazapine plus photodynamic therapy group, with 8 mice in each group. All mice received once daily with an equivalent normal saline solution, saline solution and mirtazapine (10mg/kg) respectively, orally by using metal gavage feeding needles for 42 days. Photodynamic therapy group and mirtazapine plus photodynamic therapy group received intraperitoneal injections of photosan (2mg/kg per dose). 48h following injection, tumors were irradiated with laser light. Food intake, body weight and tumor size were investigated.Results1,Experimental study of antidepressants in a pancreatic cancer xenograft mouse model: there was no significant difference in tumor size in the three groups. From the 2nd week, the food intake of mice in the mirtazapine group significantly increased compared with other two groups; the body weight of mice in the mirtazapine group at the 4th week was (16.00±1.41) g, which was higher than those in other two groups (P <0.05); from the 3rd week, the food intake of mice in the fluoxetine group significantly decreased compared with control group, and the body weight also decreased significantly from the 6th week (P <0.05); at the 6th week, the food intake of mice in the control, mirtazapine and fluoxetine groups were (3.54±0.13) g, (4.19±0.16) g and (3.34±0.13) g, and the body weight were (13.71±1.11) g, (14.86±1.68) g and (12.57±1.51) g respectively. The behavioral test in the first week, mirtazapine group exhibited a significant increase in horizontal and vertical activity compared with that in fluoxetine and control group. The grooming activity of the mirtazapine group was higher than that of fluoxetine group and control group in the second week (P﹤0.05). The difference of locomotor activity in mirtazapine and fluoxetine group disappeared during 3-6 weeks.2,Adjunctive effects of mirtazapine in a pancreatic cancer model treated with gemcitabine chemotherapy: there was no significant difference in tumor size between mirtazapine plus gemcitabine group and gemcitabine group. The tumor inhibition rates of the two groups were 69.13±2.0% and 71.6±2.4%, respectively. On days 7, the food intake of mice (4.15±0.15)g and body weight (18.34±0.78) g in mirtazapine plus gemcitabine group were slightly greater than these of (4.10±0.12)g and (18.14±0.53)g in gemcitabine group. However, no significant difference was observed. These parameters were significantly lower the food intake (4.99±0.16 )g and body weight (19.05±0.76 )g in control group. The effects of mirtazapine lasted until the end of experiment.3,Adjunctive effects of mirtazapine in a pancreatic cancer model treated with photodynamic therapy: from days 3 after photodynamic therapy (PDT), The tumor sizes of mirtazapine plus PDT group and PDT group were significantly smaller than that of control group. From the second week, tumor growth speed up again. The tumor inhibition rates of the two groups were 49%. From the 2nd week, food intake of mice was significantly increased in the mirtazapine plus PDT group (5.03±0.22)g compared with PDT group (4.87±0.15)g and control group (4.92±0.14)g (P <0.05). From the 4th week, the body weight of mice was significantly greater in the mirtazapine plus PDT group (17.13±0.83)g compared with PDT group (16.25±0.88)g and control group (16.00±0.53)g (P <0.05). The effects of mirtazapine lasted until the end of experiment.Conclusion1,Mirtazapine and fluoxetine had no significant effect on the pancreatic tumor growth. However, Mirtazapine was significantly better than fluoxetine in increasing food intake, locomotor activity and alleviating body decreasing on a pancreatic cancer mouse model.2,Mirtazapine cannot significantly enhance the effect of gemcitabine inhibiting the pancreatic tumor growth. However, to some extent, mirtazapine reversed these adverse impacts of gemcitabine chemotherapy (large dose).3,Mirtazapine cannot significantly enhance the effect of photodynamic therapy inhibiting the pancreatic tumor growth. However, Mirtazapine significantly increased food intake and alleviated weight loss in a pancreatic cancer mouse model treated with photodynamic therapy. |
PDF Full Text Request