Experimental Study Of The Anti-tumor Effect For Mice Cervical Cancer In Vivo And Its Mechanisms Of The Traditional Chinese Herbal Prescription Niuhuangtianlong Capsule

Objective: Now our mankind health is threatened by the malignant tumor .But there is no effective medicine to cure it. Niuhuangtianlong decoction has been initially proved that it has anti-tumor effects. Niuhuangtianlong capsule has the same prescription with it and has the better dosage form than it. In this study, the acute toxicity trial was done to gain the 50% lethal dose(LD₅₀) of Niuhuangtianlong capsule .The anti-tumor effect and its mechanisms were investigated, The mice bearing transplanted tumor cells of mice sarcoma S180, mice cervical cancer U14 and mice liver cancer H22 were fed with the prescription and observed the outcomes. Methods: Different concentrations of Niuhuangtianlong capsule were given to the rats at one time .Using the death number in every group, LD₅₀ was calculated by the method of Bliss. The cell strain of S₁₈₀, U₁₄ and H₂₂ were respectively transplanted into the mice to make the solid carcinoma model. The mice bearing the same tumor cells were divided into five groups : high-dose group ,middle-dose group ,low-dose group ,negative control group and positive control one .Except the positive control mice were injected with the cisplatin in their abdomens for 6 days and the negative ones were fed with NS,the other ones were fed with the corresponding prescriptions at the same time for 12 days .After 12 days ,the mice were killed at the same time ,the transplanted tumor tissues were taken out .The tumor tissues'weights were compared and the tumor inhibition rates were calculated . The expression of VEGF and MMP-9 was observed by immunohistochemistry and the NK activity was detected by the MTT method .Meanwhile the apoptotic rate was observed by the Flow Cytometry. The ascites tumour model of U14 was built to find out the influence on the life elongation of Niuhuangtianlong capsule. Results: The acute toxicity test showed the primitive prescription's half lethal dose was 55.603g/kg. The tumor inhibition rates of high-dose group,middle-dose group and low-dose group for S₁₈₀ were 47.69%, 32.93%, 25.49% (P<0.01) respectively; for H₂₂ were 50.74%, 29.65%(P<0.01), 12.80% respectively and for U₁₄ were 54.60%, 40.03%, 26.44%(P<0.01)respectively. Niuhuangtianlong capsule could significantly reduce the tumor weight of the mice with S₁₈₀ ,H₂₂ and U₁₄. The life elongations in the three trial groups with Niuhuangtianlong capsule were 101.25%, 94.58%, 8.33% respectively. Niuhuangtian-long capsule could prolong the survival time of mice with U14 tumor. The following parameters showed the immunological effect of Niuhuangtianlong capsule. The thymus index in mice with U₁₄ tumor in high-dose group, middle-dose group and low-dose group were 5.20±0.30, 4.28±0.50, 3.60±0.26; respectively ; the spleen index were 12.99±0.47 , 12.33±1.34, 11.03±0.59 respectively; the apoptotic rates were 19.79±1.75% , 13.99±2.01% and 9.87±1.31% (P<0.05) respectively .The NK activity of each group of Niuhuangtianlong capsule was significantly higher than that of the negative control group. From the low dose group to the high one, the expression of VEGF decreased, which in the three trial groups were lower than the negative control group .The expression of MMP-9 was also the same tendency. Conclusion: All the results showed that the traditional Chinese herbal prescription Niuhuangtianlong capsule has anti-tumor effects on various tumor cell lines (S₁₈₀, H₂₂ and U₁₄), and it can also improve the immune system at some degree. Its anti-tumor activity depends on drug concentration. The study proved that Niuhuangtianlong capsule could be used as a new antineoplastic agent in clinical practice. In order to use it better and safer in clinical practice in the future, the anti-tumor mechanisms of Niuhuangtianlong capsule should to be studied deeply.