Abstract
Sennoside A (SA) is a bioactive component of Rheum officinale Baill. with an activity of irritant laxative, which has been reported to possess therapeutic potential in various diseases or conditions including obesity, insulin resistance, liver steatosis, prostate cancer and pancreatic cancer progression. However, whether SA has therapeutic potential in hepatocellular carcinoma (HCC) treatment remains elusive. In this study, we treated two HCC cell lines, HepG2 and SMMC-7721 with SA and found that SA selectively inhibited the growth of HCC cells by proliferation assay. SA has a good inhibitory effect on proliferation of HepG2 cells in a concentration dependent manner, but there was no effect on SMMC-7721 cells. Then we conducted transwell assays and transcriptome analysis in HCC cells and examined the effects of SA on HCC in vivo. The results showed that SA significantly inhibited the migration and invasion of HCC. Comparison of RNA-seq transcriptome profiles from control groups and SA-treated groups identified 171 and 264 differentially expressed genes (DEGs) in HepG2 and SMMC-7721 cells respectively, in which includes 2 overlapping up-regulated DEGs and 12 overlapping down-regulated DEGs between HepG2 and SMMC-7721 cells. The qPCR were applied to investigate the transcriptional level of 9 overlapping down-regulated DEGs related to cancer metastasis, and the results were consistent with RNA-seq data. The dominate pathways including Wnt signaling pathway, TNF signaling pathway, VEGF signaling pathway, and NF-κB signaling pathway were strongly inhibited by SA, which are involved in regulating cancer metastasis. Finally, we confirmed that the downregulation of KRT7 and KRT81 could inhibit HCC metastasis. This study has provided new insight into the understanding of the inhibitory effects and potential targets of SA on the metastasis of HCC.
Highlights
Primary liver cancer was the sixth most commonly occurring cancer and the fourth leading cause of cancer death worldwide in 2018 (Bray et al, 2018)
Compared with control group (CON), Sennoside A (SA) treatment significantly inhibited migration and invasion in both Hepatocellular carcinoma (HCC) cell lines and this inhibitory effect was in a dose-dependent manner (Figure 2)
These results in vitro and in vivo suggested that SA inhibited cell migration and invasion in HCCs but may suppress HCC cell growth in a cell-type specific manner
Summary
Primary liver cancer was the sixth most commonly occurring cancer and the fourth leading cause of cancer death worldwide in 2018 (Bray et al, 2018). Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in most countries, accounting for approximately 75% of total cases (Altekruse et al, 2011). There are multimodal therapies used to treat HCC in the past several decades, including surgical resection, chemotherapy, local radiotherapy, immune and systemic treatment (Hartke et al, 2017). The therapeutic outcomes of HCC are still unsatisfactory due to post-surgical recurrence and treatment resistance. The rate of post-surgical recurrence and metastasis in HCC is extremely high (Xia et al, 2013). Clarifying the underlying mechanisms of HCC progression may provide new strategies for the diagnosis and treatment of this deadly disease
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