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Antitumor effects of DC vaccine loaded with shikonin combined with tumor cell lysate
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Abstract:
Objective: To investigate the anti-tumor effect of dendritic cells (DCs) vaccines loaded with shikonin (SK) and tumor cell lysate (TCL). Methods: DC vaccines of normal mouse origin loaded with SK and TCL were prepared in vitro. Fluorescence intensity of CD80 and CD86 on the surface of DCs was detected by flow cytometry. The expression of T-bet and RORγt in normal mouse splenic T cells co-cultured DCs that stimulated by SK + TCL was determined by flow cytometry, and the contents of IFN-γ, IL-12P70, and TNF-α in the co-culture supernatant were detected using ELISA. A Lewis lung cancer 3LL cell-bearing mouse model was established, and the mice were randomized into PBS + TCL group (PBS [1 mL] + TCL [5 × 105 cell/100 μL]), SK-L + TCL group (low SK concentration [1.25 mg/kg] + TCL), SK-M + TCL group (medium SK concentration [2.5 mg/kg] + TCL), and SK-H + TCL group (high SK concentration [5 mg/kg] + TCL), and paclitaxel (PTX) + TCL vaccine group (PTX [2 mg/kg] + TCL). Ten days after the end of vaccination, the solid tumor volume and survival rate of the mice were observed, and the killing capacity of splenic cytotoxic T lymphocytes (CTLs) was assessed by LDH assay. Results: DC vaccines loaded with SK + TCL showed high levels of CD80 and CD86 expression (both P < 0.01). The levels of IL-12P70, IFN- γ, and TNF- α in the DC-T cell co-culture supernatants were significantly increased (all P < 0.01), and the expression of T-bet and RORγt (both P < 0.01) in T cells were significantly elevated. A successful Lewis lung carcinoma mouse model was established, and the DC vaccines loaded with SK-H + TCL significantly delayed the growth of transplanted tumors and increased the mouse survival rate, while strongly inducing the cytotoxic activity of splenic CTLs (all P < 0.01). Conclusion: The SK + TCL-loaded DC vaccine can activate DCs to a mature state, up-regulate the expression of T-bet and RORγt in T cells, and initiate Th1 effector cells. SK shows promising antitumor effects in the treatment of Lewis lung carcinoma in mice.
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