Radiosensitization Effect Of Valproic Acid On Human Hepatocellular Cell Line SMMC-7221

Objective Hepatocellular carcinoma (HCC) is the third deadlymalignant tumor in the world, because of its high-recurrent,high-metastatic, poor outcome and relatively high radioresistant, it hasbeen the hot spot of tumor therapy. Radiotherapy (RT) is an importantnon-surgical strategies for killing cancer cells and prolonging thepatients’ lives. The clinical research showed that the normal hepatic cellexhibiting high sensitivity to ionzing radiation (IR). The patients oftensuffered radiation induced liver disease (RILD) induced by regulatory RT,while HCC showed high radioresistance to RT. The radiosensitivity ofHCC is associated with differentiation of cancer cells, the condition ofhypoxia, liver cancer stem cells (LCSCs), DNA Double-Stranded Breaks(DSBs) and DNA repair mechanism, MicroRNAs (miRNAs) and signalpathway. It is common phenomenon that the solid tumor contains lots ofhypoxia cancer cells. Hypoxia is the reason why tumors exhibitingradioresistance. The methods for increasing radiosensitivity contain asfollowed, increased RT doses, combined with radiosensitizer, combinedRT with chemotherapy. Valproic Acid (VPA) not only could function asanti-epileptic, but also could induce cancer cells cell cycle arrested,inhibit proliferation and promote apoptosis. VPA could increase theradiosensitivity of esophageal carcinoma cell, glioma cell and prostatecancer cell. It is still unknown that whether VPA could increase theradiosensitivity of human hepatic SMMC-7221cells. This experimentwas sought to investigate radiosensitization effect of VPA on human hepatocellular cell line SMMC-7221and its mechanism, and providereliable evidence for HCC therapy.Method MTT was used to measure the proliferation inhibitioneffects of VPA in different concentrations (0.75mmol/L,1.5mmol/L,3.0mmol/L,6.0mmol/L and8.0mmol/L) and duration (24h,48h and72h)on human hepatocellular cell line SMMC-7221. The colony formationassay was used to detect the radiosensitization of VPA. FCM wasadopted to analyze the changes in cell cycle and apoptosis level.Results The proliferation inhibition of human hepatocellular cell lineSMMC-7221was evidently restrained with a time and dose dependentmanner after24h,48h and72h treated with VPA. The IC50was41.26,9.04,2.87mmol/L. The apoptosis rate of SMMC-7221cell was largelyincreased in IR group, VPA group and VPA+IR group as compared withcontrol (P<0.05). The apoptosis rate of SMMC-7221cell in VPA+IRgroup was higher than IR group and VPA group (P<0.05). Thepercentages of cells at G0/G1phase were increased and the percentagesof cells at S phase were decreased in IR group, VPA group and VPA+IRgroup as compared with control, respectively. There was no influence onthe percentages of cells at G2/M phase.Conclusion The proliferation inhibition of human hepatocellularcell line SMMC-7221was evidently restrained with a time and dosedependent manner. VPA showed low toxic effect on SMMC-7221, butincreased radiosensitization. The mechanism of radiosensitization wasassociated with the increased level of apoptosis and cell cycle arrest.