Abstract
BackgroundBoth omacetaxine (HHT) and curcumin were shown to exhibit anti-proliferative effect on lymphoma cells. However, the role of combination of HHT with curcumin (HHT/curcumin combination) on lymphoma cells remains unclear. Thus, this study aimed to investigate the effect of HHT/curcumin combination on the proliferation, migration, and angiogenesis of lymphoma cells.MethodsCell counting kit-8 (CCK-8), Ki67 immunofluorescence and transwell assays were used to assess the viability, proliferation and migration of U937 and Raji cells respectively. In addition, tube formation assay was used to determine the effects of HHT/curcumin combination on angiogenesis in human umbilical vein endothelial cells (HUVECs).ResultsIn this study, we found that HHT/curcumin combination significantly inhibited the proliferation, migration and invasion in U937 and Raji cells (all P < 0.01). In addition, combination treatment markedly inhibited the secreted levels of vascular endothelial growth factor (VEGF)-(A-D) (all P < 0.01) in Raji cells. Moreover, combination treatment exhibited anti-tumor effects in Raji cells, as shown by the decreased signals of phosphorylated VEGF receptor 2 (p-VEGFR2) and phosphorylated protein kinase B (p-Akt) (all P < 0.01). Meanwhile, combination treatment inhibited VEGFA levels (P < 0.01) in exosomes derived from Raji cells. Application of exosomes with downregulated VEGF to HUVECs notably inhibited proliferation, migration and tube formation of HUVECs, evidenced by the decreased signals of p-Akt, angiogenin-1, matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) (all P < 0.01).ConclusionOur findings indicated that combination of HHT and curcumin could inhibit lymphoma cell growth and angiogenesis via inhibition of VEGF/Akt signaling pathway. These results suggested that HHT combined with curcumin might be regarded as a promising therapeutic approach for the treatment of lymphoma.
Highlights
Lymphomas are a heterogeneous group of lymphoid malignancies that derives from lymph gland and/or extranodal lymphoid tissue [1, 2]
These data suggested that combination of curcumin with HHT could inhibit the proliferation of lymphoma cells
Raji cells treated with HHT and curcumin led to the downregulation of exosomal VEGF; whereas additional of exogenous VEGF reversed the effect of HHT/curcumin combination on the level of VEGF in lymphoma cell-secreted exosomes (All P < 0.01; Figure 4C). These data indicated that combination of curcumin with HHT could inhibit VEGF levels in exosomes derived from Raji cells
Summary
Lymphomas are a heterogeneous group of lymphoid malignancies that derives from lymph gland and/or extranodal lymphoid tissue [1, 2]. Burkitt’s lymphoma (BL) is a highly invasive B-cell NHL characterized by a high proliferation rate of the malignant cells [5, 6]. Evidence has shown that BL is highly sensitive to chemotherapy [7]. Chemotherapy is effective in the treatment of BL but associated with unavoidable toxicity and side effects [8]. Novel strategies for the treatment of lymphomas are imminently needed. Both omacetaxine (HHT) and curcumin were shown to exhibit antiproliferative effect on lymphoma cells. This study aimed to investigate the effect of HHT/curcumin combination on the proliferation, migration, and angiogenesis of lymphoma cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
