Osteopontin siRNA does not confer resistance to toxic effects of parthenolide in Jurkat cells.

Abstract

Osteopontin (OPN) plays a critical role in cell proliferation and drug resistance in cancer treatment and hematological malignancies. In T cell acute lymphoblastic leukemia, most initial therapies can induce remission while some patients then relapse and do not respond well to chemotherapy. The sesquiterpene lactone parthenolide (PTL) can induce apoptosis in a variety of cancer cell lines via inhibition of pro-inflammatory transcription factor nuclear factor kappa B and has anti-tumor activity in acute lymphoblastic leukemia treatment. To study the role of OPN in conferring in vitro resistance to PTL in Jurkat cells. Jurkat cells were cultured with 8-20μmPTLfor48h.Transfection with OPNsiRNA was provided. Apoptosis assays were performed with AnnexinV-AlexaFluor-488/PI. Quantitative real-time polymerase chain reaction was used to measureOPNgene expression using the 2-2-ΔΔCt method. PTL has cytotoxic and apoptotic effect on Jurkat cells with IC50 values of 16.1μm, and growth inhibition effect of PTL does not differ significantly in combination withOPN-siRNA. OPN gene expression is not affected by PTL. Parthenolide induces apoptosis in Jurkat cells, but inhibition of osteopontin gene expression with siRNA does not reduce apoptotic effect of parthenolide.