Salvianolic acid A (Sal A) suppresses malignant progression of glioma and enhances temozolomide (TMZ) sensitivity via repressing transgelin-2 (TAGLN2) mediated phosphatidylinositol-3-kinase (PI3K) / protein kinase B (Akt) pathway

Abstract

Glioma originated from excessively proliferative and highly invaded glial cells is a common intracranial malignant tumor with poor prognosis. Resistance to temozolomide (TMZ) is a clinical challenge in glioma treatment due to the fact that chemoresistance remains a main obstacle in the improvement of drug efficacy. Salvianolic acid A (Sal A), originated from traditional Chinese herbal medicine Salvia miltiorrhiza , possesses anti-tumor effects and could facilitate the delivery of drugs to brain tumor tissues. In the present work, effects of Sal A on the viability, proliferation, migration, invasion and apoptosis of human glioma cell line U87 cells as well as influence of Sal A on TMZ resistance were measured, so as to identify the biological function of Sal A in the malignant behaviors and chemoresistance of glioma cells. Additionally, activation of TAGLN2/PI3K/Akt pathway in glioma cells was also detected to investigate whether Sal A could regulate TAGLN2/PI3K/Akt to manipulate the progression of glioma and TMZ resistance. Results discovered that Sal A treatment reduced the viability, repressed the proliferation, migration and invasion of glioma cells as well as promoted the apoptosis of glioma cells. Besides, Sal A treatment suppressed TAGLN2/PI3K/Akt pathway in glioma cells. Sal A treatment strengthened the suppressing effect of TMZ on glioma cell proliferation and reinforced the promoting effect of TMZ on glioma cell apoptosis, which were abolished by upregulation of TAGLN2. To conclude, Sal A treatment could suppress the malignant behaviors of glioma cells and improve TMZ sensitivity through inactivating TAGLN2/PI3K/Akt pathway.

Network pharmacology and experimental verification reveal the mechanism of safranal against glioblastoma (GBM)

“…However, not all patients respond to TMZ ( 30 , 31 ). It was previously reported that PI3K/AKT axis inhibitors could inhibit temozolomide resistance in glioblastoma cells ( 32 – 34 ), and activation of the PI3K/AKT axis could promote TMZ resistance in GBM cells ( 35 – 37 ). Therefore, we suspect that safranal and TMZ may have a synergistic effect against GBM.…”

Investigating the molecular mechanism of Mori Cortex against osteosarcoma by bioinformatics analysis and in vitro experimental

“…[ 28 ] Studies have shown that TAGLN2 is induced in the hypoxic microenvironment of glioblastoma PDX cell lines, and it enhances cellular resistance to standard treatments by binding and inhibiting PTEN, thus activating the PI3K/Akt pathway. [ 29 ] Danphenolic acid F inhibits the growth of KRAS-dependent lung cancer cells via the PI3K/AKT signaling pathway. [ 30 ] ERK is a key member of the MAPK family.…”

Hypoxia‐related THBD+ macrophages as a prognostic factor in glioma: Construction of a powerful risk model

“…Among them, RGS16, CLEC5A and TAGLN2 are key regulatory factors that promote glioma progression by activating the PI3K-AKT pathway in gliomas. [53][54][55][56] Additionally, upregulated STEAP3 in gliomas facilitates tumour cell migration and invasion and is significantly associated with immune-infiltrating cells, including macrophages and neutrophils, particularly M2 macrophages. 57 Furthermore, the highly expressed CHI3L1 in gliomas enhances NF-κB signalling by facilitating the translocation of NF-κB subunits through binding to ACTN4…”

“…Notably, EMP3, RGS16, PLAU, TAGLN2, STEAP3, CDHR1, OSMR, SERPINH1, PDPN, CHI3L1, ABCC3, SERPINE1, SOCS1, GPX8, GPNMB, CLEC5A, FOSL2, ICAM1, PRF1 and ITPRIP serve as prognostic markers for gliomas 9,41–52 . Among them, RGS16, CLEC5A and TAGLN2 are key regulatory factors that promote glioma progression by activating the PI3K‐AKT pathway in gliomas 53–56 . Additionally, upregulated STEAP3 in gliomas facilitates tumour cell migration and invasion and is significantly associated with immune‐infiltrating cells, including macrophages and neutrophils, particularly M2 macrophages 57 .…”