Effects of the Proteasome Inhibitor Bortezomib in Combination with Chemotherapy for the Treatment of Mantle Cell Lymphoma: A Meta-analysis

Objective: The efficacy and the safety of bortezomib-based chemotherapy were characterized in mantle cell lymphoma (MCL) patients. Materials and Methods: The PubMed, Cochrane Library, Clinical Key, Science Direct, Oxford Journals, and China National Knowledge Internet databases were searched up to 1 May 2019. The selected trials needed to match the inclusion criteria and be carried out to evaluate quality appraisal and the synthesis of efficacy and safety. The enrolled MCL patients using bortezomib-based chemotherapy or chemotherapy alone needed to have been compared. The overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were combined to evaluate the efficacy while serious adverse events (SAEs) (grade III-IV peripheral neuropathy, neutropenia, and infection) were used to evaluate the safety. The heterogeneity of the results were analyzed simultaneously. Results: A total of 620 patients were enrolled across four studies in our meta-analysis, and the pooled results showed that the PFS [hazard ratio (HR)=0.66, 95% confidence interval (CI)=0.54-0.82; p=0.0001)] and OS (HR=0.73, 95% CI=0.55-0.96; p=0.03) of patients with bortezomib-based chemotherapy were better than those of patients with chemotherapy alone, unlike ORR (risk ratio=1.46, 95% CI=0.85-2.49; p=0.17), while SAEs were prominent in the combination group. Conclusion: MCL patients who are ineligible for transplant or high-dose chemotherapy could benefit from bortezomib-based chemotherapy.

Lentivirus­mediated RIG­I knockdown relieves cell proliferation inhibition, cell cycle arrest and apoptosis in ATRA­induced NB4 cells via the AKT­FOXO3A signaling pathway in vitro.

Retinoic acid inducible gene I (RIG­I) is upregulated during all­trans retinoic acid (ATRA)­induced terminal granulocytic differentiation of NB4 acute promyelocytic leukemia (APL) cells. However, the function and mechanism of RIG­I in NB4 cells remains to be fully elucidated. In the present study, lentivirus­mediated RIG­I­knockdown was used to investigate the proliferation, cell cycle and apoptotic processes of ATRA­induced NB4 cells in vitro using an MTT assay and flow cytometry, respectively. The roles of RIG­I and the AKT­FOXO3A signaling pathway were investigated using western blot analysis. The results showed that the ATRA­induced expression of RIG­I was specifically and effectively knocked down at the mRNA and protein levels by lentivirus mediated RIG­I short hairpin RNA. In addition, silencing of RIG­I reduced the ATRA­induced inhibition of NB4 cell proliferation, cell cycle arrest and apoptosis. Further investigations indicated that with ATRA­induced expression of RIG­I, levels of phosphorylated (p)AKT­Thr308 and pForkhead Box (FOX) O3A­Thr32 were decreased, the expression levels of cell cycle arrest protein p27 and the apoptotic protein, tumor necrosis factor­related apoptosis­inducing ligand (TRAIL), directly transcribed by FOXO3A were increased. By contrast, following the knockdown of ATRA­induced expression of RIG­I, the levels of pAKT­Thr308 and pFOXO3A­Thr32 were increased, and the protein expression levels of p27 and TRAIL were decreased. Taken together, these results showed that the knockdown of RIG­I reduced the inhibition of cell proliferation, cell cycle arrest and apoptosis in the ATRA­induced NB4 cells via the AKT­FOXO3A signaling pathway.