The Importance Of Drug Resistance On The Biology Of Myeloma Cells

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Drug resistance against conventional therapies of cancers is an unfavorable phenomenon which reported by numerous authors (20-22). So, to overcome drug resistance in different cancers researchers have turned to use new tumor therapy approaches based on creating change in kinetic of immune modulators (15, 23, 24). In this regard, SEB is a potent superantigen which can deteriorate tumor cells through growth inhibition and apoptosis inducing. Furthermore, SEB plays critical roles against different cancers by immune responses activation (25, 26).
In the present study, we have documented that BM-MSCs are a strong factor with noticeable effects on the biology of myeloma cells. Also, BM-MSCs could change results of SEB on myeloma cell line. Furthermore,
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Furthermore, as was shown by Escobar P et al. MDA-MB-231 cells are able to induce NF-kβ signaling pathway in MSCs(37). In this notice, we analyzed expression level of IKKb molecule (a molecule belong to the canonical pathway of NF-kβ), which has attracted researcher’s attention because of its therapeutic application(38). On one hand, the expression of IKKb in co-cultured MSCs with U266 cells was up-regulated, but in presence of SEB did not show significant change. On the other hand, SEB and MSCs led to IKKb up-regulation in U266 cells, while coexistence of SEB and MSCs or SEB and C.M decreased IKKb …show more content…
Also, IL-10 can induce antibody producer B-cells proliferation. In order to effects of IL-10 on immune system, some studies introduced this cytokine as a critical force against the immune responses to the cancers (39-42). In MM, it is reported that IL-10 extensively increases the growth of myeloma cells (43-45). According to many evidence, myeloma cells and MSCs are one of the most important source of IL-10 (46-48) that our study confirmed that co-culture system increased levels of IL-10 in both of cells, maybe through NF-kβ pathway activation. Interestingly, SEB up-regulated IL-10 production in U266 cells, but down-regulated it in BM-MSCs.
Furthermore, Oh JY et al. indicated that MSCs produce TGF-β (49). Moreover, plasma cells adhesion to the stroma cells of BM induces TGF-β production (50). In addition according to Cook J and colleague study myeloma cells expressed TGF-β at a high level (51). In orchestrate with previous studies, U266 cells enhanced amount of TGF-β but the presence of U266 cells with SEB suppressed TGF-β production in BM-MSCs. Unlike to Cook J study we did not observe any significant change in TGF-β expression of U266

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