Evidence-based Exploration Of Anti-Radiotherapy/chemotherapy Of Glioma Stem Cells

Part one:Clinical trial of reversing drug resistance of glioma stem cellsObjective: ABCG2, a drug resistance gene, is proved to be only expressed on glioma stem cells. Our study has proved that nicardipine can reverse the drug resistance of ABCG2 both in vitro and in vivo. Here we try to verify it in one clinical study.Methods: One chemotherapy protocol was performed on selected patients with informed consent. Its effect was evaluated carefully.The inclusion and exclusion criteria was made at the same time.Results: Three patients were selected, among which two cases were valid and one patient was dead. In these two available cases, one patient's condition was improved obviously and the volume of tumor was diminished. The other's condition was stable. The major side effects of the chemotherapy were comprised of bone marrow depression and adverse reactions of the gastrointestinal system.Conclusion: Combined chemotherapy with Nimustine, Nicardipine and Valpoate has a determinate curative effect, and its clinical application value on glioma therapy deserved to be studied further.Part two: Exploration on radiation resistance of glioma stem cells in vivoObjective: Experiments in vitro have proved that glioma stem cells have the property of radiation resistance. We want to demonstrate that when the in vitro irradiated glioma stem cells were orthotopic transplanted in tumor-bearing mouse, this property can be still preserved.Methods: Glioma stem cells were cultured in free-serum medium and completed medium to get undifferentiated suspension neurospheres and differentiated tumor cells which were similar to the original tumor. Cells mentioned above were orthotopic transplanted into the right caudate nucleus of mice, assisted by astereotaxic apparatus after irradiance under one linear accelerator. The dose was 0 Gy, 10 Gy and 20 Gy respectively. After 21 days, brain sections were stained by HE. Cell morphology, tumor formation rate and size of transplanted tumors were observed and calculated under light microscope.Results: The tumor formation rate of un-radiated suspended neurospheres and differentiated tumor cells after transplantation were 100%(5/5). The tumor formation rate of neurospheres radiated under 10Gy were 60%(3/5),and there were no tumors observed under 20Gy. Nevertheless, the tumorigenesis ability of differentiated tumor cells was decreased after radiation. Moreover, no tumors were formed from the differentiated tumor cells radiated under 10Gy and 20Gy. The volume of transplanted tumor formed by neurospheres was much larger than that by differentiated tumor cells.Conclusion: The ability of tumorigenesis and invasion of glioma stem cells were still relatively powerful after radiation which shows the marked anti-radiation characteristic of glioma stem cells.