| Primary carcinoma of liver, which is called liver cancer or hepatoma for short, isa common malignant tumor of digestive system. It develops more in hepatitisspreading countries, such as China and Japan in Asia. The rate of hepatitis is high inour country, causing230,000deaths every year. And the new sufferers of each yearhave accounted for55%of the whole world. Liver cancer now has been a malignancyof high incidence and death rate in our country.Among all the diagnosed sufferers,80%of them are with late-stage cases ofliver cancer and it is not adaptive for them to undergo surgical tumorectomy. Forthose operation-available patients, most of them resorted to Transcatheter ArterialChemoembolization (TACE) surgery. Although surgical treatments do have sometherapeutical effect, many hepatoma patients would still have recurrence, metastasisand so on. So, searching for synthetic and effective treatment has now become anurgency in the study on primary carcinoma of liver.Chalcone compounds, with1,3-two phenyl acrylic ketone as their basic framestructure, are precursor synthesis of flavonoids in plants. Because of the greatflexibility of chalcone compound molecules, they can combine with differentbiological receptors, showing multiple pharmacological activities, such asanti-inflammation, anti-virus, anti-oxidation, analgesia, anti-AIDS, anti-depression,anti-fungus, immunosuppression and etc. Numerous studies indicate that chalcone andits derivatives have good inhibition effects on tumors. From multiple targets and inmany different ways can chalcone compounds inhibit the biological activities oftumor cells.4，-methyl-2.4-dihydroxylchalcones is a novel chalcone derivative andearlier study showed that it has a good inhibition impact on the proliferation of manytumor cells.This study combines the development of4，-methyl-2.4-dihydroxylchalconesand the research on the biological characteristics of hepatoma together, biologicallydiscussing the behavioral effects of4，-methyl-2.4-dihydroxylchalcones on theproliferation，apoptosis induction，invasion and metastasis and exploring the related therapeutic mechanism of4，-methyl-2.4-dihydroxylchalcones on liver cancer. Thisresearch will be of great significance in the development and applications of newanti-hepatoma medicine.Based on screening the inhibition effects of4，-methyl-2.4-dihydroxylchalconeson multiple hepatoma cells, this study furthered to investigate the interference of4，-methyl-2.4-dihydroxylchalcones with the biological behaviors of HCCLM3, makingdiscussion on its anti-hepatoma mechanism and laid experimental and theoreticalbasis for the biological effect of4，-methyl-2.4-dihydroxylchalcones on HCCLM3cells.1. The Inhibition Effect of4，-methyl-2.4-dihydroxylchalcones on4Types of LiverCancer CellsMethod: Growth controls of4，-methyl-2.4-dihydroxylchalcones on HepG,Bel7402, SMMC7721and HCCLM3were tested by using MTT method and IC50wasmeasured. Result:4，-methyl-2.4-dihydroxylchalcones had inhibition effects onHepG2, Bel7402, SMMC7721and HCCLM3. The concentrations of IC50were0.57,0.84,1.24and0.486μmol/L respectively. The inhibition effect on HCCLM3was theclearest which could be parallel to As2O3. Conclusion:4，-methyl-2.4-dihydroxylchalcones had inhibition effects on HepG2， Bel7402，SMMC7721and HCCLM3proliferation and worked best on HCCLM3cells.2.The Effect of4，-methyl-2.4-dihydroxylchalcones on HCCLM3ApoptosisMethod: Hochest staining and flow cytometry were employed to test the effect of4，-methyl-2.4-dihydroxylchalcones on HCCLM3apoptosis. Westernblot was usedto test the intervention effects of4，-methyl-2.4-dihydroxylchalcones on the signalingsubstances (pro-Caspase-, Bcl-2，Bαx and Caspase-3) expressions in the apoptosispathway. Result:4，-methyl-2.4-dihydroxylchalcones could induce apoptosis.4，-methyl-2.4-dihydroxylchalcones could up-regulate pro-Caspase-9expression, bαxgene expression, Caspase-3expression and down-regulate bcl-2and activate theapoptosis pathway. Conclusion:4，-methyl-2.4-dihydroxylchalcones could inhibit theproliferation of HCCLM3outside the body and induce the apoptosis.4，-methyl-2.4-dihydroxylchalcones could exert its function on bcl-2/bαx group, activated Caspase-3and induce apoptosis.3. The Effects of4，-methyl-2.4-dihydroxylchalcones on the Invasion And Metastasisof HCCLM3CellsMethod: Cell wound scratch assay and Transwell chamber model were used toobserve the effect of4，-methyl-2.4-dihydroxylchalcones on the invasion of HCCLM3cells. Result:0.4μmol/L and0.8μmol/L4，-methyl-2.4-dihydroxylchalcones hadbeen used to act on HCCLM3cells for12h, which demonstrated remarkableinhibition effect on cellular invasion（P＜0.01）. The inhibition rates of0.4μmol/Lgroup and0.8μmol/L group were40.05%and53.72%. Conclusion:4，-methyl-2.4-dihydroxylchalcones could inhibit HCCLM3cellular invasion andmetastasis outside the body. |
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