| Background:Nowadays, Cancer has become one of the important causes of human death, in which lung cancer and prostate cancer accounted for first of the U.S. men’s cancer mortality and incidence of first, an urgent need for new and effective treatment options. Inhibitors of phosphodiesterase 4 (PDE4i) in the occurrence and development of pneumonia, lung cancer, brain tumor, melanotic tumor, pancreatic cancer has inhibitory effect, but due to its gastrointestinal adverse reaction limit its clinical application, and its effect on prostate cancer unknown. In this study, we used a modified ZL-n-91 PDE4i, compared to other PDE4i, the inhibitor intensity up to 5000 times higher, and has a higher selectivity, and the side effect is small.Objective:To investigate the effect of specific PDE4 inhibitor ZL-n-91 on the development of lung cancer and prostate cancer and its related mechanism.Methods:1. Treatment of lung cancer cells and prostate cancer cells with different concentrations of ZL-n-91, to study the effect of ZL-n-91 on the growth of lung cancer cells and prostate cancer cells.2. To study the effect of ZL-n-91 with different concentrations on the migration of lung cancer cells.3. The effect of ZL-n-91 on the growth of lung cancer and prostate cancer in nude mice was studied by immunohistochemistry and other methods, using human lung cancer cell line A549, adenocarcinoma cell line PC-3.4. Using mouse lung cancer cell line LLC, the tail vein injection of LLC cells were established in primary lung cancer model. By observing the survival time of mice, pathological analysis and other research methods ZL-n-91 of lung cancer occurrence and development.Results:1. The effects of ZL-n-91 on the development of lung cancer. (1) PDE4 inhibitor ZL-n-91 dose dependent inhibition of LLC rat lung cancer cells and A549 human lung cancer cell proliferation. And when the drug concentration of ZL-n-91, LLC on the migration of lung cancer cells in mice 100uM has a significant inhibitory effect, with statistical significance. (2) after ZL-n-91 treatment, the tumor volume was significantly smaller than that of the control group. The tumor volume and weight of the drug delivery group were 1/3 times of that of the control group (32). (3) lung cancer mice were treated with different doses of ZL-n-91, with the increase of the drug dose, the number and size of lung metastases decreased, and the survival time was significantly prolonged.2. ZL-n-91 inhibit prostate cancer cell growth. (1) ZL-n-91 can inhibit the proliferation of PC-3 cells, Compared with the control group, the difference was statistically significant, and the inhibition effect was concentration and time dependent. (2) In nude mice by ZL-n-91 treatment 12 days start, give medicine group of tumor volume in mice were significantly smaller than that of the control group, to medicine for 32 days, give medicine group, the tumor volume and weight is about half of that of the control group times, and the tumor inhibition rate reached as high as 45.96%. (3) The immune group of expression of Ki67 in tumor tissue was detected, quantitative analysis of control group and to the positive rate in the treatment group respectively (40.7+0.18)%and (18.11 ± 0.06)%. The results showed that to medicine group the tumor proliferation was significantly weaker than that of the control group.Conclusion:ZL-n-91 has a significant inhibitory effect on lung cancer cell and lung cancer in mice, and ZL-n-91 has a significant inhibitory effect on the growth of human prostate cancer PC-3 cells and transplanted tumors. To provide the advantages of ZL-n-91 for clinical anti-tumor drugs, and has a good prospect of development and application. |
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