| AIMS: To investigate the anti-tumor mechanisms of matrine which including signal transduction and the expression of some drug metabolism enzymes (DMEs), and the relationship of STAT3 and DMEs.METHODS: Cultured the HepG2 cells with 0, 0.125, 0.25, 0.5, 1, 2mM Matrine or 0, 6.25, 12.5, 25, 50, 100ng/ml IL-6 for 12, 24 or 48h. then to detect the mRNA expression of STAT3 and both the protein expression of STAT3 and P-STAT3. we evaluated the CYP3A4 activity used MS-HPLC, assayed the mRNA expression of CYP450s, UGTs and stat3 by RT-PCR, detected the protein expression of CYP3A4, stat3, p-stat3 with Western-Blot.RESULTS: Matrine can significantly inhibit the expression and activation of STAT3. Matrine increased the mRNA expression of CYP2E1, UGT1A1, UGT2B and ecreased CYP3A4. 2mM Matrine increase the mRNA expression of CYP2E1, UGT1A1, UGT2B by about 10%, 90% and 20%, respectively. It also decreased CYP3A4 mRNA by about 60%, the protein expression of CYP3A4 by 80% and the activity of CYP3A4 by 90%, after treated with 2mM Matrine for 48h. 100ng/ml IL-6 can reduce the mRNA expression of CYP2E1, CYP3A4, UGT1A1, UGT2B for about 70%, and we found out the protein expression of CYP3A4 decreased 80% and the activity of CYP3A4 decreased 90%. The dependablity analysis indicated that the expression of CYP2E1, UGT1A1, UGT2B have significant association with STAT3 (R~2=0.77, 0.38, 0.43 respectively). All of these data has statistical significance.CONCLUSIONS: Matrine has an intense inhibition effect on the expression and activity of STAT3, which may be an important way for matrine's anti-tumor effects. It also increased the mRNA expression of CYP2E1, UGT1A1, UGT2B and decreased CYP3A4, inhibited the protein expression and activity of CYP3A4. and IL-6 have an opposite influence on CYP2E1, UGT1A1, UGT2B except of CYP3A4. It indicated that matrine may induce CYP2E1, UGT1A1, UGT2B through Stat3. |
