Vitamin C Selectively Inhibits Kidney Renal Clear Cell Carcinoma Cell Growth by Suppressing the HIF-1 Pathway

Aim: To observe the effect of vitamin C on Kidney renal clear cell carcinoma (KIRC) and investigate its mechanism. Methods and Results: Firstly, 29 vitamin C direct target proteins (DPTs) were identified by Drug Bank 5.0, and the protein-protein interaction (PPI) network and signaling pathways of vitamin C DPTs were analyzed. The results showed that vitamin C was not only related to KIRC, but also to the HIF-1 pathway. Meanwhile, the top 300 highly expressed genes of KIRC were obtained by GEPIA. Next, We compared the genes of four vitamin C targets in the PPI network with highly expressed genes in KIRC. Interestingly, these common genes are also involved in HIF-1 pathway. Additionally, we utilized RNA-Seq technology to explore the differentially expressed genes in KIRC with vitamin C compared to those not intervened. We observed that these differentially expressed genes exhibited a close association with hypoxia. Finally, we observed the inhibitory effect of Vitamin C on KIRC by Cell Counting Kit-8 (CCK8) assay, real-time quantitative PCR, Western blotting, flow cytometry, and colony formation assay, and confirmed that Vitamin C inhibits the growth of KIRC cells through the HIF-1 pathway. Conclusion: Through bioinformatics analyses, we identified the molecular mechanism of vitamin C’s role in KIRC and verified it through a series of experiments. Combined bioinformatics analysis will play an important role in future drug-disease interaction studies.