Glioma is among the ten most common causes of cancer-related death and has no effective treatment for it, so we are trying to find a new target for anticancer treatment. This study investigates the different expression of SRPK1 as a novel protein in glioma, which can influence tumor cells biological characteristics in normoxic and hypoxic environment. The expression levels of SRPK1 protein in glioma cell lines transfected with siSRPK1 or not were examined using immunofluorescence, RT-PCR and Western blot analysis, respectively. The impact of SRPK1 on the biological characteristics of U251 cells was further studied using methylthiazol tetrazolium assays, flow cytometry, and Transwell invasion chamber assays. The results showed that knockdown of SRPK1 inhibited tumor cells growth, invasion and migration in normoxic condition, but portion of the effect could be reversed in hypoxia. SRPK1 expression was induced in glioma cells by DDP treated, but not TMZ, in both normoxia and hypoxia conditions. We propose SRPK1 as a new molecular player contributing to the early treatment of glioma.

Gliomas, the most common primary brain tumors, have low survival rates and poorly defined molecular mechanisms to target for treatment. Serine/arginine SR protein kinases 1 (SRPK1) can highly and specifically phosphorylate the SR protein found in many tumors, which can influence cell proliferation and angiogenesis. However, the roles and regulatory mechanisms of SRPK1 in gliomas are not understood. The aim of this study was to determine the functions and regulation of SRPK1 in gliomas. We found that SRPK1 inhibition induces early apoptosis and significantly inhibits xenograft tumor growth. Our results indicate that SRPK1 affects Akt and eIF4E phosphorylation, Bax and Bcl-2 activation, and HIF-1 and VEGF production in glioma cells. Moreover, transfection of SRPK1 siRNA strongly reduced cell invasion and migration by regulating the expression of MMP2 and MMP9 and significantly decreased the volume of tumors and angiogenesis. We show here that a strong link exists among SRPK1, Akt, eIF4E, HIF-1, and VEGF activity that is functionally involved in apoptosis, metastasis, and angiogenesis of gliomas under normoxic conditions. Thus, SRPK1 may be a potential anticancer target to inhibit glioma progression.

Gliomas are one of the most common primary brain tumors in adults. They display aggressive invasiveness, are highly vascular, and have a poor prognosis. Plexin-B1 is involved in numerous cellular processes, especially cellular migration and angiogenesis. However, the role and regulatory mechanisms of Plexin-B1 in gliomas are not understood and were thus investigated in this study. By using multiple and diverse experimental techniques, we investigated cell apoptosis, mitochondrial membrane potential, cell migration and invasion, angiogenesis, PI3K and Akt phosphorylation, and also the levels of SRPK1 and αvβ3 in glioma cells and animal glioma tissues. The results indicated that Plexin-B1 expression in glioma cell lines is increased compared to normal human astrocytes. Plexin-B1 mediates RhoA/integrin αvβ3 involved in the PI3K/Akt pathway and SRPK1 to influence the growth of glioma cell, angiogenesis, and motility in vitro and in vivo. Thus, Plexin-B1 signaling regulates the Rho/αvβ3/PI3K/Akt pathway and SRPK1, which are involved in glioma invasiveness and angiogenesis. Therefore, the new drug research should focus on Plexin-B1 as a target for the treatment of glioma invasion and angiogenesis.