Introduction: Dysregulated alternative splicing is a prominent feature of cancer. The
\ninhibition and knockdown of the SR splice factor kinase SRPK1 reduces tumour growth in
\nvivo. As a result several SPRK1 inhibitors are in development including SPHINX, a 3-
\n(trifluoromethyl)anilide scaffold. The objective of this study was to treat two leukaemic cell
\nlines with SPHINX in combination with the established cancer drugs azacitidine and
\nimatinib.<\/p>\n
Materials and Methods: We selected two representative cell lines; Kasumi-1, acute
\nmyeloid leukaemia, and K562, BCR-ABL positive chronic myeloid leukaemia. Cells were
\ntreated with SPHINX concentrations up to 10\u03bcM, and in combination with azacitidine (up to
\n1.5 \u03bcg\/ml, Kasumi-1 cells) and imatinib (up to 20 \u03bcg\/ml, K562 cells). Cell viability was
\ndetermined by counting the proportion of live cells and those undergoing apoptosis
\nthrough the detection of activated caspase 3\/7. SRPK1 was knocked down with siRNA to
\nconfirm SPHINX results.<\/p>\n
Results: The effects of SPHINX were first confirmed by observing reduced levels of
\nphosphorylated SR proteins. SPHINX significantly reduced cell viability and increased
\napoptosis in Kasumi-1 cells, but less prominently in K562 cells. Knockdown of SRPK1 by
\nRNA interference similarly reduced cell viability. Combining SPHINX with azacitidine
\naugmented the effect of azacitidine in Kasumi-1 cells. In conclusion, SPHINX reduces
\ncell viability and increases apoptosis in the acute myeloid leukaemia cell line Kasumi-1, but
\nless convincingly in the chronic myeloid leukaemia cell line K562.<\/p>\n
Conclusion: We suggest that specific types of leukaemia may present an opportunity for
\nthe development of SRPK1-targeted therapies to be used in combination with established
\nchemotherapeutic drugs.<\/p>\n","protected":false},"template":"","display_control":[],"_links":{"self":[{"href":"https:\/\/ladomerylab.org\/wp-json\/wp\/v2\/research_papers\/841"}],"collection":[{"href":"https:\/\/ladomerylab.org\/wp-json\/wp\/v2\/research_papers"}],"about":[{"href":"https:\/\/ladomerylab.org\/wp-json\/wp\/v2\/types\/research_papers"}],"wp:attachment":[{"href":"https:\/\/ladomerylab.org\/wp-json\/wp\/v2\/media?parent=841"}],"wp:term":[{"taxonomy":"display_control","embeddable":true,"href":"https:\/\/ladomerylab.org\/wp-json\/wp\/v2\/display_control?post=841"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}