1.Apoptosis induced by temozolomide and nimustine in glioblastoma cells is supported by JNK/c-Jun-mediated induction of the BH3-only protein BIM.
Tomicic MT1, Meise R1, Aasland D1, Berte N1, Kitzinger R1, Krämer OH1, Kaina B1, Christmann M1. Oncotarget. 2015 Oct 20;6(32):33755-68. doi: 10.18632/oncotarget.5274.
The outcome of cancer therapy strongly depends on the complex network of cell signaling pathways, including transcription factor activation following drug exposure. Here we assessed whether and how the MAP kinase (MAPK) cascade and its downstream target, the transcription factor AP-1, influence the sensitivity of malignant glioma cells to the anticancer drugs temozolomide (TMZ) and nimustine (ACNU). Both drugs induce apoptosis in glioma cells at late times following treatment. Activation of the MAPK cascade precedes apoptosis, as shown by phosphorylation of Jun kinase (JNK) and c-Jun, a main component of AP-1. Pharmacological inhibition and siRNA mediated knockdown of JNK and c-Jun reduced the level of apoptosis in LN-229 glioma cells treated with TMZ or ACNU. Analyzing the underlying molecular mechanism, we identified the pro-apoptotic gene BIM as a critical target of AP-1, which is upregulated following TMZ and ACNU. Importantly, shRNA mediated downregulation of BIM in the malignant glioma cell lines LN-229 and U87MG led to an attenuated cleavage of caspase-9 and, consequently, reduced the level of apoptosis following TMZ and ACNU treatment.
2.Satisfactory therapy results of combining nimustine with nicardipine against glioma at advanced stage.
Lou M, Zhao Y1. J Cancer Res Ther. 2015 Oct-Dec;11(4):1030. doi: 10.4103/0973-1482.154033.
Glioblastoma multiforme (GBM) is one of the most frequent brain cancers with a very poor prognosis. According to cancer stem cell (CSC) theory, therapies that are more specifically directed against CSCs might result in much more durable responses. Recently, we treated a case of GBM basing on the conception of CSC and gained a better clinic outcome. A 37-year-old male patient complained weakness of left limbs for 1 month. Magnetic resonance imaging (MRI) showed extensive lesions in the right hemisphere. We performed an intracranial tumor partial resection and the postoperative pathological diagnose was GBM. 1 month later, he received monthly chemotherapies with the combination of nimustine and nicardipine for totally 4 times. At the last chemotherapy, MRI scan showed the cancer almost completely disappeared with significantly improved clinic condition. The combination therapy of chemotherapeutics and nicardipine may be a promising treatment for patients of GBM at advanced stage.