Journal
CELLULAR ONCOLOGY
Volume 40, Issue 3, Pages 247-261Publisher
SPRINGER
DOI: 10.1007/s13402-017-0320-1
Keywords
Glioblastoma; Shikonin; Temozolomide; Migration; Glial-to-mesenchymal transition
Categories
Funding
- Brazilian agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Brazilian agency Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Brazilian agency Fundacao de Amparo a Pesquisa do Rio de Janeiro (FAPERJ)
- Brazilian agency Pro-Saude Associacao Beneficente de Assistencia Social e Hospitalar
- Brazilian agency Ary Frauzino Foundation for Cancer Research
- Portuguese agency FEDER funds through the Operational Programme Factors Competitiveness COMPETE
- Portuguese agency National Funds through the FCT Fundacao para a Ciencia e Tecnologia
Ask authors/readers for more resources
Purpose Glioblastomas (GBM) comprise 17% of all primary brain tumors. These tumors are extremely aggressive due to their infiltrative capacity and chemoresistance, with glial-to-mesenchymal transition (GMT) proteins playing a prominent role in tumor invasion. One compound that has recently been used to reduce the expression of these proteins is shikonin (SHK), a naphthoquinone with anti-tumor properties. Temozolomide (TMZ), the most commonly used chemotherapeutic agent in GBM treatment, has so far not been studied in combination with SHK. Here, we investigated the combined effects of these two drugs on the proliferation and motility of GBM-derived cells. Methods The cytotoxic and proliferative effects of SHK and TMZ on human GBM-derived cells were tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), Ki67 staining and BrdU incorporation assays. The migration capacities of these cells were evaluated using a scratch wound assay. The expression levels of beta 3 integrin, metalloproteinases (MMPs) and GMT-associated proteins were determined by Western blotting and immunocytochemistry. Results We found that GBM-derived cells treated with a combination of SHK and TMZ showed decreases in their proliferation and migration capacities. These decreases were followed by the suppression of GMT through a reduction of beta 3 integrin, MMP-2, MMP-9, Slug and vimentin expression via inactivation of PI3K/AKT signaling. Conclusion From our results we conclude that dual treatment with SHK and TMZ may constitute a powerful new tool for GBM treatment by reducing therapy resistance and tumor recurrence.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available