| Background:Primary liver cancer is one of the most frequent clinical malignant tumors, which is a serious threat to human life health. The number of patients with Primary liver cancer in China accounts for 55% of the global total cases. Each year about 110 thousand people died of liver cancer in our country. The traditional surgery and chemotherapy and radiation therapy method have their limitations, so we need to find new ways of treating Primary liver cancer. Research shows that Heat shock protein 90 is one of the important molecules chaperone inside cellules. they have played various roles of helping protein folding, assembly and transportation, which has a significant impact on tumor growth. Recently HSP90s have become the new targets of cancer therapy. We studied the effects of 17-DMAG on human liver cancer cell lines HepG2 in our research in order to find a new way for the treatment of primary liver cancer.Objective:The aim of this study is to investigate the effect of the novel HSP90 inhibitors 17-DMAG on human liver cancer cell lines HepG2, to see proliferations or apoptosis of HepG2 after drugs and make a preliminary discussion of its mechanisms.Methods:MTT assay was applied to measure the optical density of different groups after different concentrations of 17-DMAG and DDP with HepG2 cell line. Cell growth inhibition rate and 50% inhibiting concentration(IC50) were calculated after the 17-DMAG with HepG2, which can be compared with that after DDP. We also used an optical inverted microscope to observe the morphological changes of HepG2 cell line after the drugs. In the end, Annexin V-FITC/PI double staining was to detect apoptosis rate of HepG2 cell line after 17-DMAG and DDP.Results:MTT showed 17-DMAG can suppress the proliferation and growth of the HepG2 cell lines. The rates(%) of HepG2 cell proliferation inhibition with different concentration of 17-DMAG of 100nM,250nM,500nM,1000nM and 5mg/L DDP for 24hours were respectively 15.22±1.66,23.46±1.40,37.20±2.36,48.24±1.76, 14.53±1.65.That of 48hours were 23.43±1.55,34.76±1.67,56.49±3.84,60.24±3.15,28.38±2.55.That of 72hours were 30.23±2.12,44.24±1.94,62.58±4.18,71.27±2.82,35.49±2.31.It can be showed obviously from the data that the HepG2 cell proliferation inhibition was ascending with an increasing concentration of 17-DMAG and a longer effect time. MTT showed a time-dose effect of a growing inhibition rate of HepG2 cell lines proliferation which is statistically significant (P<0.05). The inhibiting rates of 17-DMAG group above 250nm level was significantly higher than 5mg/L DDP group (P<0.05). Along with an increasing concentration of 17-DMAG, what is more, HepG2 cell density was decreased in an optical inverted microscope, the number of HepG2 cells also significantly went down. Flow cytometry analysis showed that apoptosis rate of HepG2 cell line (22.4%) was significantly higher than the normal group(0.58%) after 17-DMAG at an concentration of 400nmol/L for 48 hours (P<0.01).Compared with the apoptosis rate of DDP group (6.5%), that of the 17-DMAG group has a significant difference, which means 17-DMAG can cause apoptosis of HepG2 cell line more effectively (P<0.01),Conclusion:heat shock protein 90 inhibitors 17-DMAG have significantly inhibited human liver cancer cell lines HepG2 proliferation which showed a time-dose effect of a growing inhibition rate of HepG2 cell lines proliferation. Along with the increase of drug concentration and the extension of time, the cell proliferation ability gradually declined. 17-DMAG can induce HepG2 cell line apoptosis.17-DMAG can exert potent antineoplastic activity more effectively than DDP on human liver cancer cell lines HepG2. |
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