| BackgroundAt present, malignant tumor, heart disease and cerebrovascular are the greatest threat to human health. According to a survey conducted by Ministry of Health of China, malignant tumor incidence is higher than heart disease and cerebrovascular, and brain tumor with the high incidence of 6.3% ranks the fifth place in various kinds of tumors, only following stomach cancer, uterus cancer, breast cancer and esophagus cancer.Glioma is a common malignant brain tumor. It is difficult to completely remove glioma cells by surgery due to their invasive growth, which makes it difficult to cure. Chemotherapy drugs commonly used in clinical almost have some cycytoxicity, so it is urgent to find new chemotherapy drugs for glioma.Previous researches have proved that Ardipusilloside I has effective anti-tumor activity and does not affect glia proliferation, but its own disadvantages, such as hemolysis and difficulty in passing through blood brain barrier(BBB), restrict its delivery via intravenous administration in central nervous system(CNS). In view of this, brain interstitial chemotherapy gets our attention. Gliadel, approved by FDA in 1996, is a sustained-release BCNU wafer which targets to glioma and achieves gratifying therapeutic effect.In this study, Ardipusilloside I microspheres were prepared firstly by multiple emulsion-solvent evaporation method, and then they were directly pressed to Ardipusilloside I implants. Following that, the anti-tumor activity of Ardipusilloside I implants against rat C6 glioma cells in vitro and in vivo was futher studied. Our study will provide scientific proof for the clinical study of Ardipusilloside I implants against glioma.AimsBased on ADS-I microspheres, this study was designed to prepare ADS-I implants first, and then evaluate the anti-tumor activity in C6 cells and C6-glioma rats model.Methods1. Multiple emulsion-solvent evaporation method was taken to prepare Ardipusilloside I microspheres and then they were directly pressed to Ardipusilloside I implants.2. Sustained-release effect of Ardipusilloside I implants were tested by HPLC. MTT assay was taken to evaluate the inhibitory effects of Ardipusilloside I implants on C6 glioma cell proliferation in vitro.3. MRI was taken to observe tumor volume before and after Ardipusilloside I implants treatment on C6-glioma-bearing rats, HE staining and TUNEL staining were taken to observe the effect of Ardipusilloside I implants on glioma cells proliferation, and ELISA assay was taken to observe the effect of Ardipusilloside I implants on tumor-associated indices.Results1. Ardipusilloside I microspheres with different drug loading were prepared and then they were pressed to Ardipusilloside I implants with 3 mm diameter and 1 mm thickness for intracranial implanation.2. MTT assay of Ardipusilloside I implants release medium showed that Ardipusilloside I implants also had significant anti-tumor activity and blank implants had no cycytoxicity.3. C6-glioma rat model were established successfully, MRI showed that Ardipusilloside I implants obviously suppressed glioma growth, and significantly prolonged the survival time; HE staining and TUNEL staining showed that Ardipusilloside I implants suppressed the proliferation of glioma, induced tumor apoptosis; the levels of IL-6, CRP, TNF-α and VEGF obviously declined, but IL-2 evidently increased.ConclusionsThis study successfully prepared ADS-I implants which could implanted into rat brains via interstitial chemotherapy. Anti-tumor activity suggested that ADS-I implants could significantly suppressed C6 glioma cells proliferation in vitro, significantly suppressed rats C6-glioma growth and prolonged the survival time of tumor-bearing rats in vivo. All of this results suggested that ADS-I implants had effectively inhibitory activity against C6-glioma in vitro and in vivo. Our study will provide new directions and theoretical foundations for glioma therapy. |
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