Ginsenoside Rg1 Suppresses Non-Small-Cell Lung Cancer via MicroRNA-126-PI3K-AKT-mTOR Pathway

Abstract

As one of the most common cause of cancer death in the world, lung cancer causes approximately 1.6 million deaths annually. Among them, NSCLC accounts for approximately 85% of patients in whole lung cancer patients. Ginsenoside Rg1 has been confirmed to play an important role in various diseases including cancer. As one of miRNAs, miR-126 closely involves in pathogenesis of the several types of cancers including colorectal, prostate, bladder and gastric cancer, and so on. Thus, the present study aims to investigate effects of the Ginsenoside Rg1 on NSCLC and underlying mechanism. In the study, two lung cancer cell lines including A549 and H1650 were used. It was found that expression of miR-126 was decreased in PBMC of NSCLC patients compared to healthy control. Expression of miR-126 was decreased in cancer tissue compared to paracancerous tissues in NSCLC patients. Importantly, it was found Ginsenoside Rg1 could inhibit growth of lung cancer cells. miR-126 KD remarkably increased the expression of apoptosis genes including caspase 3 and caspase 9 and decreased cell viability in lung cancer cells including A549 and H1650 cells. Interesting, in silico analysis indicated that miR-126 could target PI3K signaling pathway, which was confirmed by WB assay. KD of PI3KR2 compromised promotion of miR-126 on cell apoptosis. Similarly, it was found that KD of mTOR compromised promotion of miR-126 on cell apoptosis. Inhibition of Ginsenoside Rg1 on growth of lung cancer cells was through miR-126 and mTOR. Thus, the present study confirmed that Ginsenoside Rg1 remarkably inhibit lung cancer, which is through microRNA-126-PI3K-AKT-mTOR pathway.

Modulation of AKT Pathway-Targeting miRNAs for Cancer Cell Treatment with Natural Products

“…In contrast, some miRNAs inhibit apoptosis in cancer cells ( Table 1 ). miR-126-3p (miR-126) silencing upregulates apoptosis gene expression and inhibits the proliferation of lung cancer cells by upregulating p-PI3K and p-mTOR expression [ 59 ]. Ginsenoside Rg1 shows antiproliferative and apoptotic effects in lung cancer (A540) cells by downregulating miR-126-3p [ 59 ].…”

“…miR-126-3p (miR-126) silencing upregulates apoptosis gene expression and inhibits the proliferation of lung cancer cells by upregulating p-PI3K and p-mTOR expression [ 59 ]. Ginsenoside Rg1 shows antiproliferative and apoptotic effects in lung cancer (A540) cells by downregulating miR-126-3p [ 59 ]. This warrants a detailed assessment of the apoptotic role of miR-126-3p and AKT signaling in ginsenoside Rg1-treated lung cancer cells.…”

Anti-cancer effect and potential microRNAs targets of ginsenosides against breast cancer

“…Ginsenoside Rg3 regulates the expression of target genes by targeting miRNAs including miR-4425, miR-603 and miR-324-5p, which in turn inhibits ovarian cancer progression ( Zheng et al, 2018 ; Lu et al, 2019 ; Lu et al, 2020 ). Ginsenosides Rh7 and Rg1 have been reported to inhibit the progression of non-small cell lung cancer (NSCLC) by targeting miR-212 and miR-126, respectively ( Chen et al, 2021a ; Chen et al, 2022 ). In particularly, several studies clarify that ginsenosides mediate the miRNAs expression profile of BC ( Li et al, 2020 ).…”

“…Notably, targeting miR-126 expression has been shown to inhibit PI3K/AKT signaling activity and thereby inhibit BC cells growth ( McGuire et al, 2015 ). Ginsenoside Rg1 can also inhibit NSCLC by targeting miR-126 to inhibit the PI3K/AKT pathway ( Chen et al, 2022 ). Therefore, we speculate that ginsenoside Rg1 may regulate the PI3K/AKT pathway by targeting miR-126, thereby inhibiting the progression of BC, which needs more experiments to confirm.…”

Bioinformatics-based prognostic analysis of non-small cell lung cancer

“…Non-small cell lung cancer(NSCLC) includes adenocarcinoma, large cell carcinoma and squamous cell carcinoma (3). Compared to small cell carcinoma, its cancer cells divide and grow more spread and slowly and metastasise relatively late (4). NSCLC accounts for about 80% of all lung cancers, and about 75% of patients are already in the middle to late stages when detected, with a low 5-year survival rate of about 7-17% (5).…”