Panoply™ Human SLC16A1 Knockdown Stable Cell Line

Cholangiocarcinoma (CCA) is a primary liver malignancy that is often diagnosed at an advanced stage. Understanding the pathogenesis of CCA and identifying novel drug resistance targets is crucial for improving clinical outcomes. Here, researchers characterized the expression of SLC16A1 in the human tumor transcriptome and proteome for the first time and found that SLC16A1 is aberrantly expressed in multiple human cancers. SLC16A1 expression levels were elevated in CCA patients with venous invasion and higher T and M stages. Furthermore, patients with elevated SLC16A1 expression had a poorer prognosis. These findings suggest an oncogenic role for SLC16A1 in CCA. Further immune infiltration analysis revealed that SLC16A1 was significantly correlated with the infiltration of cells such as neutrophils and macrophages in the tumor microenvironment, suggesting that SLC16A1 may be involved in regulating the tumor immune microenvironment in CCA. Furthermore, functional and pathway enrichment analyses revealed that SLC16A1 may influence clinical outcomes in cholangiocarcinoma patients by participating in drug metabolism. Finally, through further in vitro and in vivo experiments, the researchers confirmed that SLC16A1 acts as an oncogene in cholangiocarcinoma, promoting the growth and chemotherapy resistance of cholangiocarcinoma cells. Knockdown of SLC16A1 inhibited the growth of cholangiocarcinoma cells and enhanced their sensitivity to 5-fluorouracil (5-FU). Together, these results reveal a key role for SLC16A1 in the development of cholangiocarcinoma and highlight its importance as a potential target for improving treatment efficacy and chemotherapy sensitivity.

To investigate the impact of SLC16A1 on drug resistance, the researchers examined the effect of SLC16A1 expression on CCA cell survival in QBC939 and HuCCT1 cells treated with varying concentrations of 5-FU. CCK-8 assays showed that, compared with the control group, the survival rate of SLC16A1 knockdown cells gradually decreased with increasing 5-FU concentrations (Figures 1A-B). At a 5-FU concentration of 10 μM, SLC16A1 knockdown had no significant effect on the survival rate of either CCA cell line. However, in QBC939 cells, treatment with 5-FU concentrations of 20 μM, 40 μM, and 80 μM decreased the survival rate of control cells by 20%, while that of SLC16A1 knockdown cells decreased by 45%. In HuCCT1 cells, the survival rate of control cells decreased by 28%, while that of SLC16A1 knockdown cells decreased by 55%. Flow cytometry results showed that compared with the control group, the early apoptosis rate of SLC16A1 knockdown cells after 5-FU treatment was significantly increased (from 7.83% to 30.55%), and the survival rate was decreased (from 84.94% to 61.14%) (Figure 1C). In summary, knockdown of SLC16A1 can enhance the sensitivity of cholangiocarcinoma cells to 5-FU treatment.

Figure 1. SLC16A1 knockdown sensitizes tumor cells to 5-FU treatment in vitro. (Huang J, et al., 2024)