The Therapeutic Effect Of Tripeptide Tyroservatide (YSV) On Lung Carcinoma And Its Mechanism By Affecting Histone Acetylation

Objective:To research the anticancer effect of tripeptide tyroservatide(YSV) and to investigate its possible mechanism by affecting histone acetylation, inhibiting proliferation and inducing apoptosis in lung carcinoma A549 cells.Methods:1. The inhibiting effect of YSV on the proliferation of human lung carcinoma A549 cells was assayed by MTS method.2. The apoptosis-inducing function of YSV on human lung carcinoma A549 cells was assayed by TUNEL, DNA Ladder and FCM methods.3. The effect of YSV on cell cycle of human lung carcinoma A549 cells was assayed by FCM method.4. The effect of YSV on p21 protein and mRNA expression in human lung carcinoma A549 cells were assayed by Western Blot and Real-time PCR methods.5. The effect of YSV on acetylated histones H3 and H4 expression in human lung carcinoma A549 cells were assayed by Western Blot methods; the activity of histone deacetylase (HDAC) in human lung carcinoma A549 cells was assayed by fluorescence detection technique.Results:1. YSV(0.1～1.6mg/ml) can remarkably inhibit the proliferation of A549 cells (P＜0.05), following the increase of drug concentration and elongation of action time, the inhibition rate of YSV on A549 cells can increase gradually.2. YSV can induce the apoptosis in A549 cells, and the apoptotic cells treated with YSV are more than the control group; the DNA Ladders are detected in A549 cells treated with YSV; YSV can remarkably induce apoptosis and death of human lung carcinoma A549 cells, the apoptosis rate of YSV 0.2mg/ml, 0.4mg/ml dosages are 10.15% and 23.91% respectively, the death rate are 13.70% and 33.84% respectively (P＜0.05).3. YSV (0.2mg/ml, 0.4mg/ml) can remarkably increase the percentage of G₀/G₁ phase cells, decrease the percentage of S phase cells (P＜0.05), and the percentage of G₂/M phase cells has no change (P＞0.05).4. YSV can remarkably increase p21 protein and mRNA expression in human lung carcinoma A549 cells (P＜0.05).5. YSV can remarkably inhibit HDAC activity and increase acetylated histones H3 and H4 expression (P＜0.05).Conclusions:YSV can probably inhibit HDAC activity, increase acetylated histone expression, and then promote p21 expression, and so cell cycle of tumor cell can be affected. YSV can make A549 cells blocked in G₀/G₁ phase, inhibit DNA synthesis and cell proliferation and induce the apoptosis of tumor cell.