Effect Of Dexamethasone On Tumor Growth And The Survival Of H22 Liver Cancer Bearing Mice

IntroductionLiver cancer is a highly malignant cancer with extremely poor prognosis. The incidence is increasing year by year, and mortality is very close to incidence. However, there is still no satisfactory treatment method at present, its serious damage to human health.Glucocorticoid is one of the most common drugs in clinic, and it is closely related to the tumor treatment. It can not only anti-tumor, but also can ameliorate complications and various side effects of chemotherapy. Moreover, dexamethasone is the most commonly used glucocorticoid drugs. It not only has physiological and pharmacological effects, also is usually used for blood cancer chemotherapy drugs.In recently years, there have been lots of studies found that the glucocorticoid can inhibit solid tumor cell apoptosis. By the principle of biorelativity, we speculate that glucocorticoid should also be able to inhibit tumor cell proliferation, thus, slow down the tumor growth and progression, improve patients’ survival.Hepa22 liver cancer in mice model is the homograft model. Since the introduction into our country in 1960 s, it has been widely used in cancer research. In this study, we intend to establish the H22 ascites and subcutaneous transplantation mice tumor model, toobserve the effect of dexamethasone on growth of H22 liver cancer, the wellbeing and survival of tumor-bearing mice. The study is aimed to prove the principle that inhibiting the tumor cell apoptosis is also a way of cancer treatment, with potential to benefits the patients.ObjectivesThis research observe of dexamethasone and 5-FU effect on survival and abdominal water by establishing the H22 ascitic liver cancer mice model. Through the establishment of H22 subcutaneous transplantation liver cancer mice model, observe of dexamethasone and 5-FU effect on survival and cancer inhibitory rate. And then by flow cytometry and Realtime PCR, analysis of dexamethasone on H22 tumor cell apoptosis, cell cycle and the glucocorticoid receptor expression.Methods1. Establish H22 ascitic liver cancer, extract total RNA of ascites cells, do reverse transcriptase PCR, and make PCR amplification to confirm whether the glucocorticoid receptor is exist in H22 ascitic tumor cells.2. Selected the best suitable dosage of dexamethasone by establishing the H22 ascitic liver cancer.3. Detection of dexamethasone impact on H22 ascites tumor.4. Comparing different duration effect on H22 ascites tumor.5. Establish H22 ascitic liver cancer, extract total RNA of ascites cells, do reverse transcription PCR, and make Realtime PCR to detect whether the glucocorticoid receptor is down-regulated.6. Comparing of dexamethasone and 5-FU effect on H22 ascites tumor.7. By flow cytometry, detection dexamethasone and control group ascites cell apoptosis and cell cycle distribution.8. Establish H22 subcutaneous transplantation liver cancer, extract total RNA of tumor, doreverse transcription PCR, and make PCR amplification to confirm whether the glucocorticoid receptor is exist in H22 subcutaneous transplantation tumor cells.9.Observation of dexamethasone and 5-FU effect on H22 subcutaneous transplantation tumor.10. Establish H22 subcutaneous transplantation liver cancer, extract total RNA of ascites cells, do reverse transcription PCR, and make Realtime PCR to detect whether the glucocorticoid receptor is down-regulated.Results1. The glucocorticoid receptor was expressed in H22 ascites cells.2. The survival time of 10mg/kg dose group mice was significantly longer than the other three groups, and the ascities volume of those mice was less than 5mg/kg and 0.5mg/kg dose group mice.3. The survival times of dexamethasone group mice was significantly longer than the normal saline group, and the ascities volume was less.4. The survival of those treatment started from 5th and 6th day was significantly longer than those treatment started from 7th and 8th day after tumor cell inoculation.5. After using dexamethasone, the expression of glucocorticoid receptor was declined in H22 ascites cells.6. The survival time of dexamethasone and normal saline group mice was significantly longer than the 5-FU and the 5-FU+DEX group, but the ascities volume was more.7. After using dexamethasone, apoptosis ratio was reduced, the S phase and G2 M phase cell percentage was also declined.8. The glucocorticoid receptor was expressed in H22 subcutaneous transplantation tumor cells.9. The survival times of dexamethasone and normal saline group mice was significantly longer than the 5-FU and the 5-FU+DEX group, but the transplantation tumor were bigger.10. After using dexamethasone, the expression of glucocorticoid receptor was decline inH22 transplantation tumor cell.Conclusions1. The establishment of H22 ascitic or subcutaneous transplantation liver cancer model is successful.2. Dexamethasone can inhibit H22 ascites cell apoptosis, increase the percentage of G0G1 phase cell, decrease the percentage of S phase and G2 M phase cell. Moreover, it can down-regulate the expression of glucocorticoid receptor.3. Dexamethasone can effectively prolong the survival time of H22 ascitic liver cancer bearing mice, and using drug early is better. Compared with saline group mice, the ascites of dexamethasone group mice are less and living better. However, 5-FU can effectively inhibit ascitic cancer growth, but the survival time of mice is shorter than dexamethasone treated mice.4. The chemotherapy drug 5-FU can effectively inhibit transplantation tumor growth, but the survival benefit is very limited. Although dexamethasone has no obvious inhibitory effect on H22 subcutaneous transplantation tumor, the survival time of mice is better.