We observed no changes T-cell lymphoma in p53 protein expression. Similar changes in the c Myc pathway were also detected in ApoG2 treated HONE 1 cells, which was in agreement with the results of cell cycle analysis that ApoG2 induced cell cycle arrest in both sensitive CNE 2 cells and insensitive HONE 1 cells. Downregulation of c Myc Expression by siRNA Leads to Inhibitors,Modulators,Libraries Cell Cycle Arrest at S Phase in CNE 2 Cells Authors have reported that the oncoprotein c Myc regu lates Inhibitors,Modulators,Libraries the expression of p21 and cyclins, increases cyclin D CDK4 activity, and facilitates cell cycle progression. Also, Fan et al. found that upregulated expression of c Myc protein in NPC cells contributed to unrestricted cell pro liferation, metastasis, and tumor progression.

In our study, the immunoblots data indicated that suppression of the c Myc pathway might be responsible for ApoG2 induced cell cycle arrest in NPC cells. Inhibitors,Modulators,Libraries To test this hypoth esis, we used three siRNA oligonucleotides to knock down c Myc protein in CNE 2 cells. As shown in fig. 4A, all these three oligonu cleotides significantly suppressed the expression of c Myc protein. the reduction in c Myc expression led to upregu lation of p21 expression and downregulation of cyclin D expression. Cell cycle analysis showed that incubation with scrambled siRNA resulted in a significantly lower CNE 2 cell population arrested at S phase than did incu bation with c Myc siRNA. Compared to srambled siRNA, c Myc siRNAs induced conspicuous increasing of cells in S phase in CNE 2 cells at 48 h. Based on these results, we suggested that suppression of the c Myc pathway by ApoG2 leads directly to cell cycle arrest in NPC cells.

ApoG2 inhibites c Myc expression level in CNE 2 xenografts in nude miceTo assess the effect of ApoG2 on c Myc expression in vivo, we used the CNE 2 xenografts nude mice model. When control xenografts developed to more than 1,000 mg, all mice were euthanized Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries and tumors were dissected, weighed and fixed for immuno chemistry assay. As shown in fig. 5A and 5B, compared to NS treatment group, ApoG2 treatment provoked a significant reduction in c Myc expression level in CNE 2 xenografts. Antitumor activities of ApoG2 against CNE 2 bearing nude mice was measured by weighing the weight of CNE 2 xenografts. As shown in fig. 5D, com pared to control treatment, ApoG2 could significantly inhibit tumor weight in CNE 2 xenografts. Discussion ApoG2 is the oxidation product of gossypol and Imatinib Mesylate has two aromatic hydrocarbon quinone groups. Authors have reported that aromatic hydrocarbon quinone stimulates ROS production in hepatic cells. As we known, ele vated ROS levels may damage cellular DNA, inducing gen eration of oxidized bases, DNA strand breaks, and stop of DNA replication, in ApoG2 treated CNE 2 cells.