关键词: LSP1, Bortezomib, 药物耐受性, 凋亡

Abstract: To investigate the roles of anti-apoptosis by leukocyte-specific protein 1 (LSP1) in Multiple Myeloma cells (MM), RT-PCR and immunoblotting were used to assess the gene expression in MM cell lines, IM9 and KAS6. Plasmids containing either sh-RNA targeting LSP1 or full-length cDNA coding for human LSP1 were constructed and transfected into IM9 and KAS6 cells, respectively. Cell apoptosis rate induced by Bortezomib was measured by PI/Annexin V staining and FACS assay. The results shows that LSP1 is highly expressed in IM9 cells but undetectable in KAS6 cells and that is closely correlated with their abilities of anti Bortezomib-induced apoptosis. Knockdown LSP1 in IM9 cell leads to significant reduction of anti Bortezomib-induced apoptosis compared with its parent control cells. By contrast, overexpression of LSP1 in KAS6 cells remarkably increases its anti-Bortezomib ability compared with control KAS6 cells. RT-PCR shows that p53 is suppressed and Bcl-xL is up-regulated by LSP1 in MM cells. In conclusion, LSP1 inhibites Bortezomib-induced apoptosis in multiple myelomas by suppressing multiple pro-apoptosis genes.

Key words: LSP1, Bortezomib, drug resistant, apoptosis