Gentiopicroside suppresses cell proliferation, migration, and invasion via inhibition of the HGF/PI3K/Akt pathway in clear cell renal cell carcinoma

Abstract Clear cell renal cell carcinoma (ccRCC) is the most common malignant renal tumour; however, effective therapeutic drugs are still limited. Gentiopicroside, a naturally occurring iridoid glycoside, has demonstrated antitumour activity, but its effects on ccRCC remain unclear. This study aimed to evaluate the role of gentiopicroside in ccRCC and elucidate its underlying mechanisms. Cell viability and proliferation were measured using the CCK-8 assay, while wound healing and Transwell assays evaluated cell migration and invasion, respectively. Bioinformatic analysis of high-throughput gene expression data was performed to predict the mechanisms underlying the anti-ccRCC effects of gentiopicroside. qPCR and Western blotting were used to determine mRNA and protein levels, respectively. The results demonstrated that gentiopicroside dose-dependently suppressed proliferation, migration, and invasion of ccRCC cells. High-throughput bioinformatic analysis suggested that the PI3K/Akt pathway and HGF may mediate the regulatory effects of gentiopicroside in ccRCC. Gentiopicroside inhibited the PI3K/Akt pathway, and activation of this pathway reversed its suppressive effects on malignant phenotypes of ccRCC cells. Furthermore, gentiopicroside downregulated HGF expression, whereas HGF overexpression counteracted gentiopicroside--induced inhibition of the PI3K/Akt pathway and malignant phenotypes. In conclusion, gentiopicroside inhibits ccRCC cell proliferation, migration, and invasion via the HGF/PI3K/Akt pathway. These findings not only propose a novel candidate drug for ccRCC treatment but also advance our understanding of the bioactivity and mechanisms of gentiopicroside.