MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells

Figure 1 MK615 decreases receptor of advanced glycation end-product expression in HuH7 and HepG2 cells. Cells were plated at 1 × 10⁵/well in 24-well plates and then cultured for 24 h. MK615 was then added to the medium, followed by culture for a further 24 h. MK615 (0.1 μg/mL) decreased RAGE expression in both HuH7 (A-C) and HepG2 (D-F).

Figure 2 Proliferative effect of advanced glycation end-products on HuH7 and HepG2 cells. Cells were cultured for 24 h, and advanced glycation end-products (AGEs) (0.1 mg/mL) were then added. After 24 h, the MTT assay was performed. Glycer-AGE significantly stimulated proliferation of HuH7 cells. ss: Statistically significant.

Figure 3 Expression of endogenous receptor of advanced glycation end-product in HuH7 and HepG2 cells. Reverse transcription-polymerase chain reaction (A) and Western blotting (B) showed that HuH7 and HepG2 expressed receptor of advanced glycation end-product (RAGE) endogenously. β-actin was used as a positive control. bp: Base pairs.

Figure 4 Cell surface expression of receptor of advanced glycation end-product in HuH7 and HepG2 cells. Flow cytometry showed receptor of advanced glycation end-product expression in both HuH7 (A) and HepG2 (B).

Figure 5 MK615 does not decrease receptor of advanced glycation end-product mRNA. The concentration of receptor of advanced glycation end-product mRNA did not differ between MK615-treated HuH7 and HepG2 cells.

Figure 6 Suppression of advanced glycation end-products-stimulated growth by MK615 and apoptosis induction. A: The percentage inhibition of Glycer-advanced glycation end-products (AGE) by MK615 was significantly higher than those for the control, and Glc-AGE in HuH7 cells. In HepG2 cells, there were no significant differences among the groups. B: Frequency of apoptotic cells of Glycer-AGE by MK615 was significantly higher than those for the control, and Glc-AGE in HuH7 cells. In HepG2 cells, there were no significant differences among the groups. ss: Statistically significant.

Figure 7 Changes in percentage inhibition resulting from pre- or post-treatment with MK615. A: Cells were cultured for 24 h with MK615, and then advanced glycation end-products (AGEs) were added, followed by culture for a further 24 h. The proliferative effect of Glycer-AGE was abrogated by pretreatment with MK615 in both HuH7 and HepG2 cells; B: Cells were cultured for 24 h with AGEs, and then MK615 were added, followed by culture for a further 24 h. The proliferative effect elicited by Glycer-AGE was still evident, but was reduced. ss: Statistically significant.