The Anti-tumor Activity Of Quercetin In Multiple Myeloma

Quercetin is one of the natural flavonol compounds. Recent studies have revealed that the use of quercetin can decrease the incidence of solid rumors, such as breast cancer, prostate cancer, colon cancer and pancreatic cancer and inhibit the cell growth of these tumors. However, little study has been reported about the mechanisms of quercetin in MM. Objective1. To study the effects of quercetin on cell proliferation, apoptosis and cell cycle in NCI-H929 cells.2. To explore the effects of quercetin on proteins associated with cell apoptosis, cell cycle, ERK and AKT singal pathways. Methods:1. The cell proliferation of NCI-H929 cells was detected by MTT at the time of 0, 24,48 and 72 hours after treatment with different concentrations (0,50,100,200 umol/L) of Quercetin in vitro.2. The cell apoptosis of NCI-H929 cells was detected by Flow cytometry using with Annexin V-FITC/PI staining after treatment with Quercetin for 24 hours.3. The cell cycle of NCI-H929 cells was detected by Flow cytometry using with PI staining after treatment with Quercetin for 24 hours.4. The expressions of proteins associated with cell proliferation, apoptosis, cell cycle and other related signal pathways were detected by western blot after treatment with quercetin for 24h. Results:1. The cell proliferation of NCI-H929 cells was decreased after treatment with different concentrations (0,50,100,200 umol/L) of Quercetin in vitro(P<0.001).2. The cell apoptosis were increased by the way of dose-dependence when treated with different concentrations (0,100,200 umol/L) of Que for 24h.The rates of apoptosis were 10.77 ± 1.90%,46.23 ± 7.03% and 74.96 ± 2.57%, respectively. The difference was statistically significant between the three groups (P<0.001).3. The percentages of cells in G0/G1 phase decreased and the cells in S phase increased after treatment with Que (0,100,200umol/L) for 24h. In addition, Different concentrates of Que treatment can significantly increase the percentages of cells in G2/M phase in the way of dose-independence (9.10 ± 5.21%,20.08 ± 4.91% and 31.81 ± 5.25%). The difference was statistically significant between three groups (p<0.001).4. The activation of Caspase-3,8 and 9 accompanied with the increased cleavage of PARP and the decreased expression of Bcl-2 in NCI-H929 cells was detected.5. The expressions of P53, P21 and P27 proteins were up-regulated, meanwhile, the CDK4 protein was decreased after treatment with Quercetin.6. Different concentrations of Que could inhibit the expression of p-ERK and p-AKT in H929 cells. Conclusions:1. Que could inhibit the cell proliferation and promote apoptosis in NCI-H929 myeloma cells in vitro.2. Que induced the arrest of G2/M phase by up-regulation of p53, p21, p27 and down-regulation of CDK4, then inhibited cell proliferation and promoted apoptosis in myeloma cells.3. Que promoted apoptosis through upregulating the expression of caspase-3,-8,-9 and downregulating the expression of Bcl-2.4. Que inhibited the cell growth via inhibiting the expression of p-ERK and p-AKT in NCI-H929 cells.