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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 225 - 234 (10page)
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Purpose AMD3100, an antagonist of the CXCR4 chemokine receptor is soon to be used clinically for the peripheral mobilization of hematopoietic stem cells (HSCs) in patients with multiple myeloma. AMD3100 has been shown to activate a G protein coupled with CXCR4 and thus acts as a partial CXCR4 agonist in vitro. Thus, we explored whether AMD3100 affected the survival and proliferation of myeloma cells in vitro.
Materials and Methods The effects of AMD3100 on survival and proliferation of two myeloma cell lines (RPMI8226 and U266) as well as CD138+ cells obtained from several patients with multiple myeloma were analyzed by flow cytometry using annexin V and a colorimetric cell proliferation assay (CCK-8 assay).
Results AMD3100, but not T140, another CXCR4 antagonist, stimulated the proliferation of myeloma cell lines and CD138+ primary human myeloma cells (-2-fold increase) in a dose-dependent manner in serum-free culture for up to 5 days, which was inhibited by pretreating the cells with pertussis toxin. AMD3100 enhanced the proliferation of U266 cells induced by interleukin-6 and partially reversed AG490-mediated growth inhibition and apoptosis induced by serum deprivation in RPMI8226 cells. AMD3100 induced the phosphorylation of Akt and MAPK p44/p42 in U266 cells and MAPK p44/p42 in RPMI8226 cells. In contrast, AMD3100 markedly increased the cell apoptosis and reduced the number of RPMI8226 cells after 5 to 7 days of culture under serum-free conditions.
Conclusion AMD3100 exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of myeloma cells, signaling via CXCR4 in vitro.
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참고문헌 (22)
참고문헌 신청
Azab AK / 2009 / CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy /
Diamond P / 2009 / Targeted disruption of the CXCL12/CXCR4 axis inhibits osteolysis in a murine model of myelomaassociated bone loss / J Bone Miner Res 24 : 1150 ~ 1161
Durig J / 2001 / Differential expression of chemokine receptors in B cell malignancies / Leukemia 15 : 752 ~ 756
Grignani G / 2005 / Clinical use of AMD3100 to mobilize CD34+ cells in patients affected by non-Hodgkin's lymphoma or multiple myeloma / J Clin Oncol 23 : 3871 ~ 3872
Guleng B / 2005 / Blockade of the stromal cell-derived factor-1/CXCR4 axis attenuates in vivo tumor growth by inhibiting angiogenesis in a vascular endothelial growth factor-
Diamond P / 2009 / Targeted disruption of the CXCL12/CXCR4 axis inhibits osteolysis in a murine model of myelomaassociated bone loss / J Bone Miner Res 24 : 1150 ~ 1161
Durig J / 2001 / Differential expression of chemokine receptors in B cell malignancies / Leukemia 15 : 752 ~ 756
Grignani G / 2005 / Clinical use of AMD3100 to mobilize CD34+ cells in patients affected by non-Hodgkin's lymphoma or multiple myeloma / J Clin Oncol 23 : 3871 ~ 3872
Guleng B / 2005 / Blockade of the stromal cell-derived factor-1/CXCR4 axis attenuates in vivo tumor growth by inhibiting angiogenesis in a vascular endothelial growth factor-
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