| Malignant tumor is one of the most major desease which seriously threaten human health.The morbidity and mortality of tumor are both high.To deal with malignant tumor which can not be surgical excision or prevent the recrudescence of malignant tumor which has already been surgical excision,chemotherapy is still the main methods of treatment. But conventional chemotherapeutics have some disadvantage such as selective differential, toxicant and side effect are high.Long use has led to drug fast.Seeing the safety,effective and less adverse drug is important.Thalidomide(THD),one kind of Glutamic acid derivatives which was used to treat Pregnancy vomiting,but has finally been removed from the market because it has the teratogenic effects in the 1960s,has been discovered to be effective in some treatment for some autoimmune diseases.Recent research reveals that THD is a potential antitumor drug. It can play the role of malignant tumor through inhibiting new blood vessels produce, regulating the immune function,etc.This article emphasizes the antineoplastic effect and its mechanism of Thalidomide by in vivo and in vitro.Points are as follows.1.Antineoplastic effect of Thalidomide in vitroWe detect the inhibition played by thalidomide on proliferation of liver cancer cell strain cultured in vitro using MTT.Thalidomide in the dose of 6.25-100μmol·L-1 has inhibition on both mice HepA and S180 tumour cell lines cultured in vitro and human HepG2 and HL60 tumour cell lines cultured in vitro.The higher the concentration is,the stronger the effect has,with a clear dose-effect relationship.The inhibitory effect of different cell lines is different,the IC50 values are:65.0,70.3,56.4和54.4μmol·L-1.Treat with tumor respectively by using Thalidomide in combination with 5-fluorouracil in the dose of 6.25,25,100μmol·L-1.and observe the growth of cell afer 12,24,36,48 and 60 hours respectively,we finally find that the effect of Thalidomide on tumor cells has an obvious time-response relationship,the longer time,the stronger effect after 12-48h,the time-response curve of all groups are similar.2.The antihepatocarcinoma effect of Thalidomide in vivo.The administration injection of Thalidomide for 13 consecutive days has the significantly inhibition in the growth of the HepA and S 180 neoplastic mice,the inhibition rates of Thalidomide in the dose of 20,40,80mg·kg-1×13d were 28.1%,38.7%,52.3% (HepA) and 26.1%,30.4%,47.8%(S180).In addition,the use of Thalidomide can significantly prolonged the survival time of HepA hepatocellular carcinoma model mice, the survival extended rates of Thalidomide 20,40,80mg·kg-1 were 26.2%,51.8%,94.4% (HepA) and28.6%,44.5%,66.0%(S180).3.The research on the Anti-hepatoma mechanisms of ThalidomideThe HepG2 cells with the treatment by the thalidomide show typical changes in tumor cell apoptosis behind electron microscopy.Apoptotic cells of which the volume is reducing, can be seen that their chromatin condense to dense and distribution become a crescent-shaped along the nuclear membrane.Advanced apoptosis cell can be seen that the cells decompose into apoptotic bodies coated with the cell membrane.With DNA labeling, flow cytometry make analysis of apoptosis change.While Thalidomide 6.25-100μmol L-1 act on HepG2 for 48 hours,apoptosis rate rise from 9.3%up to 35.5%percent,showing a significant concentration-dependent. the use of Thalidomide 20,40,80 mg·kg-1 significantly increased the spleen index of HepA liver cancer mice,Thalidomide 20,40,80mg·kg-1 significantly increases the proliferation of spleen lymphocytes induced by HepA liver cancer mice ConA,LPS. Besides,Thalidomide 40,80mg·kg-1 significantly increases the production of IL-2 and the activity of NK cell inside liver cancer mice,inhibit the abnormally high content of IL-6, TNF-αand NO.4.conclusionThalidomide has an evident effect in defending the antineoplastic effect both inside and outside body.The mechanism may be related with increasing the death and withering of the tumour cell,accommodating the function of the immunity.
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