All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro

Abstract

Abstract. All-trans retinoic acid (ATRA) is a derivative of vitamin A that can induce differentiation and apoptosis, as well as inhibit proliferation, in glioma cells. However, the effect of ATRA on the migration and invasiveness of glioma remains poorly understood. In addition, although it is universally accepted that ATRA can induce apoptosis and inhibit proliferation in glioma cells, the association between the concentration and effects of ATRA remain unclear. Therefore, the present study investigated the effects of ATRA treatment on the migration, invasion, apoptosis and proliferation of glioma cells. The U87 and SHG44 glioma cell lines were treated with various concentrations of ATRA, consisting of 0, 5, 10, 20 and 40 µmol/l. A scratch wound healing assay and a Matrigel invasion assay were used to investigate cell migration and invasion, respectively. Flow cytometry was performed to investigate apoptosis and cell cycle distribution. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to investigate the expression of matrix metalloproteinase (MMP)-2 and -9 in each cell treatment group. Following treatment with ATRA, the migration, invasion and proliferation of the glioma cells were significantly inhibited, and the apoptosis rate was significantly increased compared with that of the blank control group. Furthermore, a dose-effect association was identified between each effects and ATRA treatment. The mRNA and protein expression of MMP-2 in U87 glioma cells was not significantly affected following treatment with low concentrations of ATRA, consisting of 5 and 10 µmol/l ATRA, compared with the expression in the control group (P>0.05). However, treatment with high concentrations of ATRA, consisting of 20 and 40 µmol/l ATRA, significantly downregulated the expression levels of MMP-2 in U87 cells. In contrast to U87 cells, the administration of ATRA treatment to SHG44 glioma cells resulted in a significant and dose-dependent downregulation in MMP-2 mRNA and protein expression (P<0.01). In addition, significant downregulation of MMP-9 expression was identified in the two glioma cell lines (P<0.01). The results of the present study indicate that treatment with ATRA may inhibit migration, invasion and proliferation, and promote apoptosis in glioma cells. Furthermore, the current study indicates that the inhibition of glioma cell invasion by ATRA may be partially associated with its effect ability to downregulate MMP expression.

All‐trans retinoic acid eluting poly(diol citrate) wafers for treatment of glioblastoma

“…As demonstrated in our work and others, ATRA causes differentiation of U87MG cells into fibrous astrocytes (Das et al, ; Karsy, Albert, Tobias, Murali, & Jhanwar‐Uniyal, ; Liang, Yang, & Guo, ; Shi et al, ). However, we demonstrated evidence of differentiation with ATRA released from a polymeric wafer rather than ATRA added to culture medium.…”

ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

“…Previous studies on the effect of ATRA on MMPs are overlapping and contradictory. While some studies show that ATRA upregulates MMPs 38 , others reported an opposite effect for ATRA in different cell types 39 40 41 . A possible explanation for this divergence is that ATRA exerts its effect by binding to different isoforms of the RARs, alpha, beta and gamma.…”

Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice

“…Due to different dosages, atRA can not only promote, but also inhibit, the proliferation of cells [18]. It has been reported that atRA treatment may inhibit the proliferation of glioma cells [19] and mouse embryonic palatal mesenchymal cells [16,17]. atRA-induced proliferation and survival has also been assessed in lung cancer cells [20,21], chicken primordial germ cells and neuronal cells [22].…”