Forsythoside B suppresses glioblastoma by upregulating the expression of PTPRN

Glioblastoma (IDH-wildtype) (GBM), the most common high-grade glioma, is a highly invasive and malignant tumor in the brain. Currently, there is no effective treatment for GBM, highlighting the urgent need to find novel therapeutic drugs. Forsythoside B (FB), as a phenylethanoid glycosides compound extracted from Forsythia suspensa, has shown pharmacological functions such as anti-inflammation and anti-bacteria. However, its effects and mechanisms in GBM remain unclear. By performing several in vitro assays, we found that FB suppressed the proliferation of GBM cells in dose- and time-dependent manners. Furthermore, FB arrested the cell cycle at the G0/G1 phase and induced apoptosis in GBM cells. FB also significantly inhibited GBM cells migration. Mechanistically, RNA sequencing results showed that FB treatment remarkably upregulated the expression of PTPRN (a protein-coding gene that plays an important role in the progression of various cancers) in GBM cells. Consistent with this finding, PTPRN expression was downregulated in GBM samples from the Chinese Glioma Genome Atlas (CGGA) and other databases. Knockdown of PTPRN partially restored the inhibitory effects of FB on GBM cells, whereas, overexpression of PTPRN enhanced FB-induced suppression of GBM cell growth and migration. Finally, we found that FB slowed down the growth of tumor in a GBM orthotopic mice model through upregulating PTPRN expression in vivo, with no significant toxicity to other organs. Taken together, these results suggest that FB exerts its anticancer effects on GBM via increasing the expression of PTPRN, which may provide a potential new therapeutic strategy for the treatment of GBM.