changes in protein profiles in bortezomib applied multiple myeloma ...

which then permits NF-κB to enter the nucleus and mediate transcription. After NF-κB
translocates to the nucleus, it initiates the transcription of a wide range of genes that
promote cell survival and growth, influences the expression of cell adhesion molecules
and cytokine signaling and decreases apoptosis susceptibility. All of these molecules are
of great significance in cancer progression (Orlowski and Baldwin, 2002; Voorhees et
al., 2003; Richardson et al., 2003) (Figure 1.11).
Figure 1.11. The inhibition of NF-κB activation.
(Source: Richardson et al., 2003)
The NF-κB pathway is constitutively active in some cancer cells, especially in
MM. If NF-κB is inhibited by I-κB, cancer development is prevented. The role of
Bortezomib in NF-κB pathway is to inhibit both NF-κB activation by protecting I-κB
from degradation by the 26S proteasome and the adhesion of MM cells to bone marrow
stromal cells (BMSCs), bringing about blockade of the adhesion related transcription
and then secretion of multiple cytokines (Chauhan et al., 2005) (Figure 1.12).
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