changes in protein profiles in bortezomib applied multiple myeloma ...
changes in protein profiles in bortezomib applied multiple myeloma ...
changes in protein profiles in bortezomib applied multiple myeloma ...
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CHAPTER 5<br />
CONCLUSIONS<br />
Multiple Myeloma is a malignant plasma cell disorder and the second most<br />
common hematological disorder (Dalton et al., 2001). Unfortunately, its <strong>in</strong>cidence is<br />
<strong>in</strong>creas<strong>in</strong>g day by day. Chemical agents and natural products which may have strong<br />
anticancer potential always attract the attention of cl<strong>in</strong>icians and basic science<br />
researchers. Bortezomib is one of them, known as proteasome <strong>in</strong>hibitor that has entered<br />
cl<strong>in</strong>ical trials for Multiple Myeloma (Mateos and Miguel., 2007). Until now, the effect<br />
mechanism of Bortezomib on Multiple Myeloma has been tried to expla<strong>in</strong> by molecular<br />
level but, to the best of our knowledge, there is no any studies has been pursued about<br />
the <strong>changes</strong> <strong>in</strong> prote<strong>in</strong> <strong>profiles</strong> of Bortezomib <strong>applied</strong> Multiple Myeloma cells (U-266)<br />
<strong>in</strong> the literature. It has a vital significance to <strong>in</strong>vestigate prote<strong>in</strong> <strong>profiles</strong> <strong>in</strong> terms of<br />
understand<strong>in</strong>g the dynamic alterations of cellular prote<strong>in</strong>s for diagnostic and therapeutic<br />
options.<br />
In this study, it was demonstrated anticancer potentials (both cytotoxic and<br />
apoptotic effects) of Bortezomib on human MM U-266 cells. In addition to this, we<br />
have identified the differentially expressed prote<strong>in</strong>s of U-266 cells when they exposed<br />
to Bortezomib with an enough concentration, for the first time. Because the function of<br />
the differential expressed prote<strong>in</strong>s are of great importance for new targeted teurapautic<br />
options both Multiple Myeloma and other cancer types.<br />
In order to achieve our aims <strong>in</strong> the project, variety of multidiscipl<strong>in</strong>ary subjects<br />
came together. Cancer research techniques, biochemical studies and proteomics were<br />
comb<strong>in</strong>ed. Prote<strong>in</strong> profil<strong>in</strong>g provides a much better understand<strong>in</strong>g of an organism, <strong>in</strong><br />
terms of structure and function. Use of prote<strong>in</strong> profil<strong>in</strong>g <strong>in</strong> the study of <strong>multiple</strong><br />
prote<strong>in</strong>s, prote<strong>in</strong> forms, and prote<strong>in</strong> families almost always by compar<strong>in</strong>g two different<br />
states (diseased vs. healthy or treated vs. untreated) is expected to expand our<br />
understand<strong>in</strong>g of molecular mechanisms. At the first experiment part, the cytotoxic<br />
effect was determ<strong>in</strong>ed by measur<strong>in</strong>g the IC50 value of Bortezomib at 72 h us<strong>in</strong>g XTT<br />
cell proliferation assay. It was calculated from cell proliferation plots and found to be 17<br />
nM. Then, apoptosis was evaluated by measur<strong>in</strong>g the <strong>changes</strong> <strong>in</strong> caspase-3 enzyme<br />
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