Acid ceramidase confers radioresistance to glioblastoma cells

作者：Doan Ninh B^*; Nguyen Ha S; Al Gizawiy Mona M; Mueller Wade M; Sabadini Roger A; Rand Scott D; Connelly Jenifer M; Chitambar Christopher R; Schmainda Kathleen M; Mirza Shama P

来源：Oncology Reports, 2017, 38(4): 1932-1940.

DOI：10.3892/or.2017.5855

• glioblastoma
• acid ceramidase
• acid ceramidase inhibitors
• carmofur
• radioresistance
• radiation
• sphingosine
• sphingosine-1-phosphate
• Sph-1P
• deoxyribonucleic acid
• DNA

Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy of the central nervous system. The standard treatment protocol, which involves surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ), still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or progression, developing resistance to standard treatment. This study demonstrates that GBMs acquire resistance to radiation via upregulation of acid ceramidase (ASAH1) and sphingosine-1- phosphate (Sph- 1P). Moreover, inhibition of ASAH1 and Sph- 1P, either with humanized monoclonal antibodies, small molecule drugs (i. e. carmofur), or a combination of both, led to suppression of GBM cell growth. These results suggest that ASAH1 and Sph- 1P may be excellent targets for the treatment of new GBMs and recurrent GBMs, especially since the latter overexpresses ASAH1. Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy of the central nervous system. The standard treatment protocol, which involves surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ), still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or progression, developing resistance to standard treatment. This study demonstrates that GBMs acquire resistance to radiation via upregulation of acid ceramidase (ASAH1) and sphingosine-1-phosphate (Sph-1P). Moreover, inhibition of ASAH1 and Sph-1P, either with humanized monoclonal antibodies, small molecule drugs (i.e. carmofur), or a combination of both, led to suppression of GBM cell growth. These results suggest that ASAH1 and Sph-1P may be excellent targets for the treatment of new GBMs and recurrent GBMs, especially since the latter overexpresses ASAH1.

• 出版日期2017-10