Experimental Study On Anti-tumor Effect Of Compound NBAM

Malignant tumor is one of the major diseases that is a serious threat to human health and life. In recent years, the incidence is increasing year by year. The treatment of malignant tumors has a variety of ways, but chemotherapy is still the main treatment for it. The development of the good specificity, high efficiency, low toxicity of anti-tumor drugs has become a hot issue in the area of drug research. In this study, the selected compound NBAM through structural modification of amantadine is a new type of compounds that has not been reported.This paper discusses issues such as the inhibitory effect of NBAM on SMMC-7721 human hepatoma cell line, the acute toxicity of NBAM in normal mice and the anti-tumor effect of NBAM on H22 tumor bearing mice to explore the mechanism of anti-tumor by experimental methods in vitro and in vivo, and the detailed contents are as follow:The toxicity of NBAM on normal cell: the MTT assay was used to detect the toxicity of NBAM in vitro. The results indicated that the toxicity of NBAM on the normal liver cell line HL-7702 in vitro is lower than the fluorouracil.The inhibitory effect of NBAM on SMMC-7721 human hepatoma cell line: The methods of MTT and colony formation were used to study the anti-tumor activity of NBAM in vitro. Results of the MTT showed that dealt with the compound NBAM for 48h, the SMMC-7721 human hepatoma cell line had shown different levels of inhibition compared with the control group from 6.25 mg/ L to 200mg/L(P <0.05). The maximum inhibition rate is 58.57% and the 50% inhibiting concentration (IC50) is 52.64 mg / L. Results of the colony formation showed that the compound NBAM had inhibitory effect to SMMC-7721 human hepatoma cell line with the control group from 12.5mg / L to 200mg / L. The toxicity of NBAM in normal mice: The LD50 of NBAM was 1444.2mg/kg, which was detected by oral acute toxicity experiment. This result showed that the compound NBAM is a low toxicity compound according to toxicology grading standards.The anti-tumor effect of NBAM on H22 tumor bearing mice: the H22-bearing mice were used to detect the anti-tumor effect of NBAM in vivo. The experimental results showed that compared with the control group, the compound NBAM could inhibit tumor growth in the H22-bearing mice, and the highest inhibition rate is 51.03%. The compound NBAM can increase the number of white blood cells (WBC) and nucleated cells in bone marrow, and do not change the DNA content in bone marrow significantly, and excludes damage to the spleen, kidney and thymus. And it can enhance the SOD activity in tumor-bearing mice and reduce the MDA content of tumor-bearing mice by high-dose and medium-dose. The method of morphological observation of the H22 solid tumor was used to investigate the anti-tumor mechanism of NBAM in vivo, pathological pictures were seen in obvious morphological changes of apoptosis. The anti-tumor mechanism of NBAM may be tumor cells apoptosis and cell cycle arrest.Conclusion: The compound NBAM had lower toxicity and better anti-tumor activity in both vitro and in vivo. The anti-tumor mechanism of NBAM may be as follows: NBAM may inhibited the growth of the tumor cell; NBAM could stimulate the activity of the immune cell to enhance immune function and improve anti-oxidant capacity to remove oxygen free radicals, which plays an auxiliary and indirect anti-tumor effect.