Combination therapy using parthenolide and doxorubicin induces apoptosis in Raji cells: insights into miR-27b and signaling pathway alterations.

Abstract

Burkitt lymphoma, a highly aggressive form of non-Hodgkin lymphoma, have significant treatment challenges, such as chemotherapy-related toxicity and the risk of relapse, especially in older adults. Treatment of Raji cells, a Burkitt lymphoma cell line, with parthenolide in combination to doxorubicin may enhance therapeutic efficacy. This study aimed to evaluate cell viability and apoptosis following treatment with these agents, and to investigate the underlying molecular mechanisms involving miR-27b and the MET/PI3K/AKT signaling pathway. Raji cells were treated with varying concentrations of parthenolide and doxorubicin for 48 and 72 h, cell viability was assessed using the MTT assay, and apoptosis was quantified using flow cytometry. Subsequently, we performed quantitative RT-PCR to evaluate the expression levels of miR-27b, MET, PI3K, and AKT. The half-maximum inhibitory concentration (IC₅₀) values of 976.1 nM for doxorubicin and 4.39 µM for parthenolide were determined at 48 h. The apoptosis rate increased from 7.6% in the untreated control to 44.5% and 49.2% for doxorubicin and parthenolide, respectively, reached to 81.2% at higher doses of parthenolide in combination (p < 0.001). miR-27b expression was significantly upregulated, particularly in the combination group (p < 0.001). MET and PI3K expression was significantly downregulated by the combination treatments (p < 0.05). In conclusion, combination of parthenolide and doxorubicin exert enhanced cytotoxic effects via increased apoptosis and modulation of miR-27b and the MET signaling pathway in Raji cells, regulatory relationship between miR-27b and the MET signaling pathway may contribute to the observed therapeutic benefits. Further research is required to clarify the molecular mechanisms and therapeutic applications of this combination strategy.