Inhibitory effect of targeted fusion peptide IL-4Rα-lytic on primary effusion lymphoma
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Abstract:
Objective: To explore the in vitro and in vivo cytotoxicity of fusion peptide IL-4Rα -lytic against Kaposi sarcoma- associated herpesvirus (KSHV) positive primary effusion lymphoma (PEL) cells and its safety. Methods: The cytotoxicity of IL-4Rα-lytic against KSHV + PEL cells (BCBL-1 and BCP-1) was measured by MTT assay. The IL-4Rα-lytic induced apoptosis of KSHV + PEL cells was analyzed by FCM. A BCBL-1 cell xenograft mice model was constructed. IL-4Rα-lytic was intraperitoneally injected for three consecutive weeks (3 times/week), and the inhibitory effect of IL-4Rα-lytic on the growth of BCBL-1 cell xenograft in mice was evaluated with in vivo bioluminescence imaging technology. Moreover, the toxic side effect was analyzed using H-E staining and whole blood cell analysis. Results: Fusion peptide IL-4Rα-lytic had a selective cytotoxicity against KSHV + PEL BCBL-1 and BCP-1 cells (all P<0.01) and could rapidly kill KSHV + PEL cells (all P<0.01). IL-4Rα-lytic could induce the apoptosis of KSHV + PEL BCBL-1 and BCP-1 cells (all P<0.05). IL-4Rα-lytic significantly inhibited the growth of BCBL-1 cell xenograft in mice(P<0.05) without causing obvious organ toxicity (all P<0.05) and abnormal changes in body weight (P>0.05). Conclusion: Fusion peptide IL-4Rα-lytic can significantly inhibit the growth of KSHV + PEL cells in vivo and in vitro without obvious toxic side effects, which is expected to provide a novel strategy for the treatment of PEL.