Ginsenoside Rg3 suppresses ovarian cancer cell proliferation and invasion by inhibiting the expression of lncRNA H19

Abstract

Ovarian cancer (OC) is the most malignant disease of the female reproductive system and accounts for a large proportion of gynecological cancer-related deaths. Emerging evidence has indicated that ginsenoside Rg3, one of the tetracyclic triterpenoid saponins in ginseng, plays crucial roles in regulating cancer progression, yet its role and mechanisms in regulating the proliferation and invasion of OC are still elusive. In this study, the cell viability, proliferation, migration and invasion of OC were assessed by using methyl thiazol tetrazolium (MTT), colony formation, wound healing and Transwell assays, respectively. The protein levels of E-cadherin and N-cadherin were analyzed by Western blot assay. The expression of long noncoding RNA (lncRNA) H19 was analyzed by quantitative real-time polymerase chain reaction (RT-qPCR). The results revealed that ginsenoside Rg3 significantly inhibited the viability of OC cells (SKOV3 and A2780) in a concentration‑dependent manner. Ginsenoside Rg3 (50 μg/ml) had almost no significant effect on the activity of human ovarian epithelial cells (HOSEpiCs). Thus, this dose was selected for the subsequent experiments. Furthermore, Rg3 markedly decreased the colony formation, migration and invasion of OC cells. In addition, the expression of N-cadherin was downregulated, and the expression of E-cadherin was upregulated with Rg3 treatment. Moreover, lncRNA H19 was upregulated in OC cells, and Rg3 negatively regulated H19 expression in a concentration-dependent manner. In terms of the mechanism, knockdown of H19 inhibited cell proliferation, migration and invasion, while overexpression of H19 reversed the inhibitory effect of Rg3 on the OC cells. In conclusion, ginsenoside Rg3 suppresses the proliferation, migration and invasion of OC cells by partially inhibiting the expression of lncRNA H19.

Ginsenoside Rg3 alleviates the migration, invasion, and angiogenesis of lung cancer cells by inhibiting the expressions of cyclooxygenase‐2 and vascular endothelial growth factor

“…The resistance of LC cells to conventional therapy and targeted therapy is attributed to EMT (Raoof et al, 2019), so preventing EMT process has become an important approach for LC treatment (Tulchinsky et al, 2019). A previous research identified that Rg3 downregulates the protein level of N-cadherin, but upregulates that of E-cadherin in ovarian cancer cells (Zhao et al, 2021). Rg3 also reduces the expression of vimentin in human cutaneous squamous cell carcinoma (Zhang et al, 2019).…”

Transcriptome Analysis of the Anti-Proliferative Effects of Ginsenoside Rh3 on HCT116 Colorectal Cancer Cells

“…Many studies have examined the effects of Rh2 on different tumor cells and documented that it inhibited cell proliferation, induced apoptosis, and arrested the cell cycle [ 23 , 24 , 25 , 26 ]. Other tetracyclic triterpenoids, such as ginsenoside Rg3 [ 27 ], Rg5 [ 28 ] and compound K [ 29 ], can also inhibit tumor cell proliferation. These results suggested that the tetracyclic triterpene ring of these compounds may be responsible for their anti-tumor function.…”

Long noncoding RNA H19 in ovarian biology and placenta development

“…62 Also, ginsenoside Rg3, one of the tetracyclic triterpenoid saponins in ginseng, reduced the Warburg effect in ovarian cancer cells 66 as well as the proliferation and invasion of the cells via the downregulation of H19. 65,66 These reports indicate that H19 is a potential therapeutic target for treating ovarian cancers.…”

“…64 Also, the knockdown inhibited the proliferation and invasion of ovarian cancer cells, with evidence of E-cadherin upregulation and N-cadherin downregulation in the cells. 65 Additionally, a reduction of H19 expression in a subcutaneous nude mice model of ovarian cancer resulted in the inhibition of tumor growth 53 while H19 suppression reduced glucose consumption and lactate production in ovarian cancer cells. 66 Pyruvate kinase muscle isozyme M2 (PKM2), which is known to promote cellular glucose uptake, lactate production, and cancer metastasis, 67 was also downregulated in the H19-depleted cells via the upregulation of miR-324-5p.…”

“…The apoptosis of the cells was increased through the downregulation of Bcl‐2 and the upregulation of Bax, caspase‐3, and caspase‐9 64 . Also, the knockdown inhibited the proliferation and invasion of ovarian cancer cells, with evidence of E‐cadherin upregulation and N‐cadherin downregulation in the cells 65 . Additionally, a reduction of H19 expression in a subcutaneous nude mice model of ovarian cancer resulted in the inhibition of tumor growth 53 while H19 suppression reduced glucose consumption and lactate production in ovarian cancer cells 66 .…”