Current treatment options of
glioblastoma include
chemotherapy and limited surgical resection.
Temozolomide (TMZ) is the current therapeutic choice for
chemotherapy. Still, it has severe limitations due to the development of resistance that occurs by genetic modification and constitutive activation of several cell signaling pathways. Therefore, it is essential to develop combination
therapy of TMZ with other novel compounds to prevent the development of chemo-resistance. In this study, we used two inhibitors; ICA, an inhibitor of PKC-ι and ζ-Stat, an inhibitor of PKC-ζ. T98G and U87MG
glioblastoma cells were treated with either ICA or ζ-stat or TMZ monotherapies, as well as TMZ were combined with either ICA or ζ-stat for five consecutive days. Our in vitro results exhibited that ICA when combined with TMZ, significantly decreased the viability of cancerous cells compared with untreated or TMZ or ICA monotherapies. Additionally,
glioblastoma cells were remarkably undergoing apoptosis against the combination treatment of TMZ and ICA
nucleotide compared with untreated control cells, as suggested by our
Annexin-V/PI flow cytometric analysis. Moreover, the combination of TMZ and ICA also decreased the invasion of
glioblastoma cell lines by acting on FAK/
Paxillin pathway, as evidenced by scratch assay, transwell invasion assay, Western blot and immunoprecipitation analysis. Furthermore, our in vivo data presented that the combination of ICA and TMZ also reduced
glioblastoma tumor growth and volume in mice. These data suggest that atypical
PKCs, particularly PKC-ι might be an important therapeutic target as adjuvant
therapy in the treatment of
glioblastoma.