Ionizing Radiation Changes Moesin Expression In Glioblastoma And Affects Liferation And Metastasis

Gliomas are tumors with glial differentiation characteristics,which are classified as grade I-IV by world health organization(WHO),and glioblastoma(GBM)is the most malignant glioma.The prognosis of GBM is often poor due to its high invasiveness and relapses.At present,the treatment of glioma is often based on surgical treatment,postoperative concurrent chemotherapy and radiotherapy as an adjuvant therapy.Studies have shown that surgical treatment has some limitations due to the inconspicuous boundary between glioma and normal tissue,complex nerve distribution in the brain,and postoperative complications.Chemotherapeutic agents are also frequently used in the treatment of gliomas,and temozolomide was the first chemotherapeutic agent proven to be effective for GBM,but it may also elicited some problems,such as cell drug resistance,hematotoxicity and tumor recurrence.For low-grade gliomas,radiotherapy can play a key role in controlling disease development and symptom presentation,but for high-grade gliomas,especially GBM,radiotherapy could not inhibit the development of the disease even using the higher radiation dose,and the tumor showed radioresistance.By literature consulting,carbon ion radiotherapy is expected to improve the effect of treating glioma,and in previous studies,it was also found that carbon ion irradiation of GBM cells reduced cell proliferation and migration.Moesin(MSN)plays a very important role in the development of glioma.The up-regulation of MSN will significantly increase the proliferation,invasion and migration of glioma cells.However,it is unclear that MSN expression effects on the GBM cell proliferation,metastasis and invasion after irradiation.In this study,we firstly used analyzed the relationship between MSN expression and clinicopathological parameters and survival of glioma patients.Then the expression changes of MSN at m RNA and protein levels in GBM cells were detected after X-rays and carbon ion irradiation by q PRC and Western Blot,respectively.Next,the expression of MSN was knockdown using si RNA,and cell proliferation,metastasis and invasion were analyzed after cotreatment X-ray irradiation and si RNA through CCK8,wound-healing assay and transwell.Finally,we explored the effect on cell proliferation and migration after carbon ion irradiation.The results showed that:1.Bioinformatics analysis revealed that the expression of MSN in clinical samples of glioma patients was correlated with WHO grade,histological type of glioma,and age of initial diagnosis of patients,however,it has no correlation with gender and whether it is primary/recurrent cancer.For patients with WHO grade I-IV as a whole,patients with high MSN expression often have a poor prognosis;2.X-ray irradiation enhanced the expression of MSN in GBM cells,while carbon ion irradiation inhibited it.Moreover,the trends of MSN expression depended on the dose of irradiation;3.Compared with X-ray irradiation alone,X-ray irradiation combined with MSN knockdown treatment significantly inhibited the proliferation and migration of GBM cells;4.Cell proliferation was attenuated and cell turning angle was alleviated when GBM cells were irradiated with carbon ion beams,suggesting that carbon ion could inhibit GBM metastasis.These results discovered there were the differentiated responses in GBM after different radiotherapeutic beams from MSN aspect,suggested a new kind of molecular mechanism showed the biologic advantage of carbon ion radiotherapy,also implied the patients with GBM will have a good response if they treat with carbon ion radiotherapy.