Human SLC2A9 adenoviral particles

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Although the mechanisms of HCC progression are not well understood, recent studies have suggested the potential contribution of the uric acid transporter SLC2A9 to tumor suppression. Here, researchers found that SLC2A9 expression was reduced in human HCC tissues and cell lines. Moreover, overexpression of SLC2A9 inhibited HCC cell proliferation. SLC2A9 induced apoptosis in HCC cells by inhibiting the expression of caspase 3. The study also showed that upregulation of SLC2A9 reduced the accumulation of intracellular reactive oxygen species (ROS). In addition, SLC2A9 increased the mRNA and protein expression of the tumor suppressor p53 in HCC cells. Probenecid inhibited SLC2A9-mediated uric acid transport, promoted HCC cell proliferation, inhibited apoptosis, induced intracellular ROS, and reduced the expression of p53 in HCC cells. Therefore, this study suggests that SLC2A9 may be a novel tumor suppressor gene and a potential therapeutic target for HCC.

Here, the researchers conducted flow cytometry experiments to investigate the effect of SLC2A9 on cell apoptosis. The results showed that in HepG2, apoptosis was observed after SLC2A9 adenovirus (Adv-SCL2A9) transfection, while apoptosis was reduced in the probenecid group (Figure 1). In addition, the proportion of apoptotic cells in the Adv-SLC2A9 group (44%) increased compared with the negative control group (20%), while the proportion of apoptotic cells in the probenecid group (10%) decreased compared with the negative control group (20%) (Figure 1B). Caspase 3 is closely related to cell apoptosis. Therefore, Western blotting was also performed to detect the mRNA and protein expression of caspase 3. The results showed that SLC2A9 increased the mRNA and protein expression of caspase 3 (Figure 1C and D). Probenecid decreased the mRNA and protein expression of SLC2A9. These data indicate that SLC2A9 induces apoptosis in HCC HepG2 cells.

Figure 1. SLC2A9 induces cell apoptosis in HepG2 cells. (Han X, et al., 2019)