Experimental Study On Anti-tumor Effect Of Pyrimidine Borotungstate

Malignant tumor is one of the major diseases affecting persons' health and the invasion and metastasis of malignancy will threaten patients' lives at last. Traditional therapenutic tools and drugs are not efficient to certain malignancy. So we must develop and utilize effective drugs against tumors. Polyoxometalates have been reported that have distinctive biology activity and anti-tumor activity. Pyrimidine borotungstate (PBT) is a new type compound of polyoxometalates with keggin structure. We study the effect of PBT on anti-tumor in vivo and vitro to disclose the mechanism of anti-tumor.1.1 MTT method was used to examine the anti-tumor activity of PBT against several human cancer cells ( SMMC-7721 cells, SGC-7901 cells,Hela cells ).The result showed that PBT could inhibit the growth and proliferation of human carcinoma cells. The IC50 were 57μg/ml,209μg/ml,193μg/ml respectively. Furthermore, it was able to kill SMMC-7721 cell significantly.1.2 MTT method was used to examine the cytotoxicity of PBT in human normal FL cell. The result showed that no toxic activities in low concentration but cytotoxicity was displayed in the range of 800～1600μg /ml ,the highest inhibition rate was 32.29%.1.3 3H-TdR method was assayed the inhibition of PBT on DNA synthesis of SMMC-7721 cell. The result displayed that the inhibition rate would become higher with the increase of concentration.1.4.1 We detected the apoptosis of SMMC-7721 cell by FCM. The apoptosis rate in low ,middle concentration groups were significant greater than control group (p<0.05), but the high concentration group had no effect of inducing apoptosis. we also analyzed the cell cycle and the result displayed that G0/G1 stage cells were significantly greater in low,middle concentration groups than that in control group and S stage cells were significant lower than that in control group. 1.4.2 The cell morphology of SMMC-7721 cell was observed under fluorescence microscope. The picture displayed the features of apoptosis, such as fragmented nuclei and apoptotic bodies.2.1 we counted the median lethal dose (LD50) of PBT by acute toxicity test by mouth in mice. The value was 1117.38mg /kg and the range of 95% confidence limit was 911.59-1369.6mg/kg. It indicated that PBT was a low toxic material.2.2 The bearing tumor mice with hepatoma-22 was established for anti-tumor experiment. PBT was administered by p.o and divided into 3 groups, that were 25mg/kg, 50mg/kg, 100mg/kg. After 12 days treatment with PBT, Low, middle and high dose groups inhibition rate (IR) in H22 were 20.32%,33.15%,52.94% respectively. The IR in high dose group was not lower than 5-Fu group.2.3 Gotten blood from caudal vein of tumor mice and counted WBC value. The result showed that WBC value was higher in low dose group than that in control group(P<0.05)and the WBC value of other dose groups of PBT had no significant variation. But the WBC value of 5-Fu group was much lower than any other groups(P<0.05). It indicated that PBT has no influence on blood function, no inhibition on spinal.2.4 The spleen index of low, middle dose groups were higher than that of control group(P<0.05), but the high dose group had no significant variation. The thymus index of low dose group was higher than that of control group(P<0.05), but the middle and high dose groups had no significant variation. The both index in 5-Fu group were lower than that in other groups(P<0.05). 2.5 The incremental reaction of mouse lymphocyte was observed by the activity of spleen cell to mitosis ConA. Result showed that PBT of low and middle dose groups had the effect of improving the lymphocyte conversion.2.6 FCM method was used to detect the apoptosis rate of spleen cells and thymus cells of tumor mice. The result showed that low dose PBT could inhibit the apoptotic of spleen cells. Three doses PBT can also inhibit the apoptosis of thymus cells of tumor mice to protect mass thymus cells not die.The result showed the efficient anti-tumor of PBT in vitro and in...