| Glioblastoma multiforme (GBM) got its notorious reputation from its fatal end result, and well known vicious course of action. The difficulty to manage and control this primary brain tumor has lead to its very poor prognosis and low survival rate over the past decades. With this in mind, scientists are struggling to find a cure for this tumor. Among these approaches that are currently being tried by scientist are combination therapy, immunotherapy, vaccine therapy, and gene therapy. Combination therapy approach is considered one of the most promising types of treatments to overcome these aggressive tumors, and bring some progress in the standard of care and prognosis. In this project we used combination therapy to achieve these goals. By using silibinin and SAHA as agents to downregulate survivin and sensitize the cell lines that we used in this project to the action of standard well known cancer drugs mainly Temozolomide, etoposide, and CPT-11. The cell lines we used have been chosen due to the difference in their genetic mutations. LN229 cell line is mutated at p53 (heterozygous mutation), U87 cell line is mutated at PTEN, and A172 cell line is mutated at PTEN and p53. Also we used TMZ-resistant LN229 cell line. The methods we used are Western's blot analysis, MTT cell viability assay, Trypan blue dye exclusion analysis, and colony forming assay. Our results showed different response from different cell lines to these combination therapies. Interestingly, combination of silibinin and TMZ showed a dramatic effect on LN229 cell line with viability brought down to 20% as compared to the control. Silibinin is well known as a safe drug, well tolerated by patients, and non toxic even at high doses. Silibinin is the agent of choice to bring down survivin to the lowest level possible, and sensitizes tumor cells to the action of standard drugs mainly Temozolomide. Our results support current changing paradigm of cancer therapy, whereupon "cancer" is considered to be a multitude of diseases that require individualized treatment as a function of specific malignancy-inducing mutations. Thus, combination of Silibinin with TMZ and, especially, with etoposide was effective with LN229, but not with U87 or A172 cells that have different mutations. |
