STAT3 silencing for enhanced sensitivity of malignant glioma cells to carmustine

摘要

Malignant glioma, the most common type of primary central nervous system (CNS) cancer, has consistently proven unresponsive to chemotherapy. This is due partly to the physiological barriers in place to protect the brain from outside infection and partly due to the changes in gene expression that typify pathogenesis in glioma. One example of such a change in gene expression is the constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3). Constitutively activated STAT3 expression is prevalent in glioma; furthermore, evidence exists that shows the level of STAT3 expression may be positively correlated with the grade of the cancer [5]. In this work, the human glioma cell lines A172 and U87 were tested for their expression of STAT3. Once it was determined that both cell lines showed significant STAT3 expression, the cells were assayed to determine whether knockdown of STAT3 alone has an effect on cell viability as well as whether it increases the cells' response to carmustine, an alkylator type chemotherapeutic. The knockdown of STAT3 through the use of short interfering RNAs was found to decrease the viability of both U87 and A172 glioma cell lines in vitro, and further to increase their sensitivity to carmustine.