20(S)‐ginsenoside‐Rg3 reverses temozolomide resistance and restrains epithelial‐mesenchymal transition progression in glioblastoma

Nov 16, 2018Cancer science

20(S)-ginsenoside-Rg3 may reverse drug resistance and slow cell changes linked to spread in aggressive brain tumors

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

20(S)-ginsenoside-Rg3 effectively downregulated expression in glioma cell lines.

MGMT is associated with resistance to (TMZ) in glioma cells.
20(S)-Rg3 may enhance the sensitivity of glioma cells to TMZ treatment.
The downregulation of MGMT by 20(S)-Rg3 occurs through the Wnt/β-catenin pathway.
20(S)-Rg3 exhibited no significant cytotoxicity at effective doses in vivo.
The compound also significantly inhibits the progression of (EMT) in glioma cells.

AI simplified

Glioblastoma multiforme (GBM) is one of the most malignant human intracranial tumors. (TMZ) is the primary alkylating agent for GBM patients. However, many GBM patients are resistant to TMZ. Therefore, patients with GBM urgently need more effective therapeutic options. 20(S)-ginsenoside-Rg3 (20(S)-Rg3) is a natural chemical with anti-tumor effects, but at present there is little understanding of its functional mechanism. Several research reports have demonstrated that (MGMT) repairs damaged DNA and contributes to TMZ resistance in gliomas. In addition, recent studies have shown that MGMT gene expression could be regulated by the Wnt/β-catenin pathway. However, whether 20(S)-Rg3 inhibits MGMT expression and augments chemosensitivity to Temozolomide (TMZ) in glioma cells remains unclear. In this study, we explored the modulating effects of 20(S)-Rg3 on MGMT. We used glioma cell lines, primary cell strain (including T98G, U118 and GBM-XX; all of them are MGMT-positive glioma cell lines) and xenograft glioma models to examine whether 20(S)-Rg3 increased the sensitivity to TMZ and to reveal the underlying mechanisms. We found that the MGMT expression was effectively downregulated by 20(S)-Rg3 via the Wnt/β-catenin pathway in glioma cell lines, and TMZ resistance was significantly reversed by 20(S)-Rg3. Meanwhile, 20(S)-Rg3 shows no obvious cytotoxicity at its effective dose and is well tolerated in vivo. In addition, we found that 20(S)-Rg3 significantly restrains the (EMT) progression of glioma cells. Taken together, these results indicate that 20(S)-Rg3 may be a novel agent to use in treatment of GBM, especially in TMZ-resistant GBM with high MGMT expression. 6

Key numbers

200 μmol/L

IC50 of 20(S)-Rg3

Half maximal inhibitory concentration for glioma cells treated with 20(S)-Rg3.

250 μmol/L

IC50 of

Half maximal inhibitory concentration for glioma cells treated with .

15.6%

Early apoptosis percentage

Percentage of early apoptotic glioma cells treated with 20(S)-Rg3 and .

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text (PDF) ↗View full text (XML) ↗View full text ↗

20(S)‐ginsenoside‐Rg3 reverses temozolomide resistance and restrains epithelial‐mesenchymal transition progression in glioblastoma

Abstract

Key numbers

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Key numbers

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief