**6.3. IAP**

In CD133 + cells isolated from glioblastoma an increased mRNA expression of livin, survivin and the multidrug resistance-associated protein 1 (MRP1) was detected. Therefore, the effects of etoposide, a pro-apoptosis agent, on these associated protein genes in glioblastoma stem-like cells have been studied. Results showed that after etoposide treatment, glioblastoma CSCs displayed a stronger resistance to apoptosis and death. The anti-apoptotic gene livinβ was more related with the high survival rate and MRP1 was more related with transporting chemotherapeutic agent out of glioblastoma stem-like cells [228]. In pancreatic cancer it has been demonstrated that targeting XIAP by RNAi inside the cancer cells, the combination of TRAIL with MSCs suppressed metastatic growth in these tumours [229]. Recently, it has been demonstrated that survivin is regulated by the interleukin-4 (IL-4) pathway in colon CSCs. Blockage of IL-4-mediated signaling pathway with leflunomide, Stat6 inhibitor, increased the nuclear survivin pool suggesting that the IL-4/STAT-6 pathway could escape cell death. IL-4 neutralization, mediated by STAT-6, could down-regulate survivin expression and localization, increasing the nuclear pool and in this way inducing chemo-sensitivity of CSCs [230].
