| Liver cancer is still a threat to human health, high degree of malignancy and poor prognosis. Early surgery is the best treatment options, but few people seize the opportunity, the survival of the advanced primary liver canner without treatment is about 1-4 months. Thus it is particularly important to search the safe and reliable non-surgical therapy, to develop the efficient anticancer drugs and to improve the quality of life about patients with advanced liver cancer. And it is the goal of cancer researcher. After endless research, not only the uses of drug but also drug delivery methods have made significant progress. the clinical application of interventional treatment of liver cancer is now being recognized the preferred method at home and abroad. Including the Transcatheter hepatic arterial chemoembolization(TACE), liver through the skin injection, laser heat treatment, Cryotherapy, radioisotope intervention, cryotherapy, and traditional Chinese medicine Interventional treatment. It is obtained better results by percutaneous injection of Chinese medicine to cure the advanced hepatocellular carcinoma in recent years. This kind of Chinese medicine is toxic, such as norcantharidinit and Arsenic Trioxide, is confirmed a good anti-tumor effect in vitro and vivo experiments.Arsenic trioxide (As2O3) is extracted from Chinese medicine arsenic, the first for the treatment of acute promyelocytic leukemia, and later extended to solid tumors of liver cancer. Confirmed by experimental and clinical, the exact effect of tumor is efficacy. Anti-tumor effects of As2O3 have a concentration, time-dependent relationship between a certain ranges at the higher drug concentration, the longer the medication, the effect the better. However, its therapeutic dose is near to toxic dose, when larger doses greater toxicity. synthesis of low concentration of As2O3 can be increased local drug dose and prolonged treatment to improve the effect of the slow release of drugs and reduce side-effects on the human body. Poloxamer 407 (P407) is a new type of drug release material which has a non-ionic polymer surfactant, low toxicity, small irritation and good biocompatibility. It is an ideal new drug controlled release carrier, which can be used as anti-cancer drug carrier. And it delays the drug release and enhances the effect of anti-cancer. In this experiment, the transplantation tumor nude mice model of human hepatocellular carcinoma was established, the P407 was as a controlled-release drug carrier and together with As2O3 to made As2O3 sustained-release preparations for tumor injection. Contrast with the conventional formulations As2O3, to explore whether or not the sustained-release preparations had the anti-tumor effects which had low concentration and minor side effects.Nude mice were subcutaneously transplanted with human HepG2, when the tumor of bearing cancer nude mice reached about 0.5 cm in diameter, and then randomly divided into 3 group as experimental group, positive control group and blank control group. Test group: the nude mice were treated by As2O3-P407, positive control group: the nude mice were treated with As2O3. We inject pure 2mg/kg As2O3 (According to commonly used clinical dose of 10 mg/d converted to dose in nude mice)into the two groups of nude mice, about 0.03-0.04ml evey mice. and blank group: the nude mice were treated with the same volume of NS. Injection was injected into nude mice every four days one time. In one whole period of treatment nude mice was injected four times. After one period of treatment, the therapeutic effects of three groups were compared. The therapeutic effects contain the weight of the nude mice, the changes of tumor size, the inhibitory rate of tumor. After slices of tumor tissue were prepared, HE staining , TUNEL assay and Transmission Electron Microscope observation were carried out. According to these results, the situation of the tumor cells apoptosis was detected.After the bone marrow smears of hind femur were prepared, the situation of myelosuppression was observed. The situations of survivance, mental status, activities, the response of stimulate, the decrease of body mass, appetite, urine and stool were observed after the treatment. the quality of life about nude mice and the drug toxicity were evaluated according to the results.The results of this experiment as follows:The growth about the tumor of the As2O3-P407 treatment group was significantly inhibited; the size of the tumor was significant smaller than the As2O3 treatment group (P<0.05); the weight of the two groups'humor were significant different: 0.3±0.08g and 0.6±0.2g (P<0.05). The weight of the blank group was 1.1±0.1 and compare with the other two groups, the difference was all significant (P<0.05). The inhibitory rate of humor about As2O3-P407 treatment group and As2O3 treatment group were 72% and 46%. The weight of the As2O3-P407 treated nude mice was heavier than the other two groups, and the difference was significant (P<0.05).Bone marrow suppression phenomenon was not observed. All three groups of nude mice survived. The nude of experimental group, positive control group had good state about active,responsive to stimuli,good appetite and stool forming; the blank group nude had low spirit, less activity, insensitive to the stimulus and decreased the body mass.Conclusion: intratumoral injection with As2O3-P407 can maintain the active drug density and extend the action time in tumor, Its curative effect is better than merely As2O3 administration.
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