2019 Fiscal Year Annual Research Report
Investigation of putative roles for GSK3b in glioblastoma stemness phenotype and the underlying biological mechanisms
| Project/Area Number |
18K16553
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| Research Institution | Kanazawa University |
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Principal Investigator |
Pyko Ilya 金沢大学, がん進展制御研究所, 博士研究員 (00731853)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | glioblastoma / temozolomide / GBM stem-like cells / GSK3β |
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| Outline of Annual Research Achievements |
Studies in vitro and in animal model were carried out complementary to optimize treatment of glioblastoma (GBM) by enhancing anti-tumor effect by combination of GSK3β inhibition and temozolomide (TMZ). For in vitro study, we examined effect of GSK3β inhibition and TMZ on patient derived GBM stem-like cells (SCs). I found that GSK3β inhibition enhances effect of TMZ against GBM-SCs and participate in regulation of GBM stemness phenotype. For animal model study, I have developed software pharmacokinetics model and determined optimal concentration of GSK3β inhibitor for continuous intra-tumor infusion by subcutaneous pumps for treatment of orthotopic GBM models and examined the effects of continuous intra-tumor infusion of GSK3β inhibitor, against GBM in mice bearing human GBM-SCs. Our experiments showed that GSK3β inhibition is effective for treatment of experimental GBM generated by inoculation of most malignant GBM-SCs characterized by shortest survival in control animals. We investigated biological mechanisms by which GSK3β regulate GBM stemness phenotype and revealed changes in stem cell markers’ expression in GBM-SCs under GSK3β inhibition, which can be associated with regulation of GBM stemness phenotype by GSK3β via multiple signaling pathways.
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