Fengbo Yu1, Guihong Li2, Junxia Gao3, Yuxue Sun2, Pengfei Liu2, Haijun Gao2, Peiwen Li2, Ting Lei2, Yong Chen2, Ye Cheng2, Xiao Zhai4, Arash J Sayari5, Haiyan Huang2, Qingchun Mu6. 1. School of Pharmacy, Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, 157011, China. 2. Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China. 3. Department of Emergency, Hongqi hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, 157011, China. 4. Department of Orthopaedics, Changhai Hospital Affiliated to the Second Military Medical University, Shanghai, 200433, China. 5. Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033, USA. 6. Department of Neurosurgery, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, 157011, China.
Abstract
OBJECTIVES: Glioblastoma multiforme (GBM) is the most aggressive brain tumour type in humans. Its poor prognosis is largely attributed to its invasiveness and high rate of recurrence. Recurring GBM is commonly resistant to chemotherapeutic drugs, making it specially difficult to treat. Recent studies have revealed that matricellular glycoprotein SPOCK1 to be upregulated in several cancer types and to be specifically expressed in invasive GBM, but not in other types of non-invasive brain tumour, which prompted us to study the mechanism of action of SPOCK1 in invasion, recurrence and drug resistance of GBM cells. MATERIALS AND METHODS: SPOCK1 expression in GBM tissues was evaluated using qPCR, Western blotting and immunohistochemical staining. Cell migration was tested by the wound healing method and cell invasion was assessed using transwell plates with Matrigel coating. Western blotting was performed for E-cadherin, vimentin, N-cadherin, p-Akt and Akt. Cell viability was examined using the MTT assay. RESULTS: We found that the expression of SPOCK1 was significantly upregulated in recurrent GBM. We also demonstrated that SPOCK1 positively regulated migration, invasion and EMT process of GBM cells. Furthermore, SPOCK1 mediated TMZ resistance in GBM, as knockdown of SPOCK1 expression in TMZ-resistant GBM cells substantially sensitized these cells to TMZ. CONCLUSION: SPOCK1 results were positive and it mediated TMZ resistance in GBM. In addition, SPOCK1 regulated invasion and TMZ resistance in GBM cells via the Akt signalling pathway.
OBJECTIVES:Glioblastoma multiforme (GBM) is the most aggressive brain tumour type in humans. Its poor prognosis is largely attributed to its invasiveness and high rate of recurrence. Recurring GBM is commonly resistant to chemotherapeutic drugs, making it specially difficult to treat. Recent studies have revealed that matricellular glycoprotein SPOCK1 to be upregulated in several cancer types and to be specifically expressed in invasive GBM, but not in other types of non-invasive brain tumour, which prompted us to study the mechanism of action of SPOCK1 in invasion, recurrence and drug resistance of GBM cells. MATERIALS AND METHODS:SPOCK1 expression in GBM tissues was evaluated using qPCR, Western blotting and immunohistochemical staining. Cell migration was tested by the wound healing method and cell invasion was assessed using transwell plates with Matrigel coating. Western blotting was performed for E-cadherin, vimentin, N-cadherin, p-Akt and Akt. Cell viability was examined using the MTT assay. RESULTS: We found that the expression of SPOCK1 was significantly upregulated in recurrent GBM. We also demonstrated that SPOCK1 positively regulated migration, invasion and EMT process of GBM cells. Furthermore, SPOCK1 mediated TMZ resistance in GBM, as knockdown of SPOCK1 expression in TMZ-resistant GBM cells substantially sensitized these cells to TMZ. CONCLUSION:SPOCK1 results were positive and it mediated TMZ resistance in GBM. In addition, SPOCK1 regulated invasion and TMZ resistance in GBM cells via the Akt signalling pathway.
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