Ipilimumab affectsTlymphocytesandBcl-2mRNAexpression in xenograft tissues of lung cancer-bearing mice by inhibiting TGF-β1/ERK signaling pathway / 中国肿瘤生物治疗杂志

ABSTRACT

@# Objective: To study the effect of ipilimumab on T lymphocytes and Bcl-2 mRNA expression in lung cancer-bearing mice by inhibiting TGF-β1/ERK signaling pathway. Methods: Forty-five C57 mices inoculated with Lewis lung cancer cells were randomly divided into control group, low dose ipilimumab group and high dose ipilimumab group with 15 mice in each. The low and high dose groups were given 3 mg/kg and 5 mg/kg ipilimumab respectively, while the control group was given 0.9% sodium chloride solution with the same volume. The effects of ipilimumab on TGF-β1/ERK signaling pathway, Bcl-2 mRNA expression, immune function improvement and tumor inhibition in three groups were detected by WB and qPCR. Results: After administration of ipilimumab, the tumor weight and volume of mice in low-dose and high-dose groups were significantly lower than that of the control group, and the tumor inhibition rate increased in a dose-dependent manner (P<0.05). The thymus index and spleen index of mice were significantly higher than that of control group, which also increased in a dose-dependent manner (P<0.05). The levels of CD3+, CD4+, CD4+/CD8+ cells in the high and low dose groups were significantly higher than those in the control group, with significantly higher levels in high dose group compared with the low dose group (P<0.05). The levels of serum inflammatory factors were significantly lower than those in control group, and the levels of serum TNF-α, IL-6 and IL-3 in the high dose group were significantly lower than those in the low dose group (P<0.05). The expressions of TGF-β1, ERK1/2, p-ERK1/2 and MEK in tumor tissues of both high and low dose groups significantly decreased, with more lower levels in high dose group than in low dose groups (all P<0.05), and the positive rate of TGF-β1 expression in high dose group was the lowest. The mRNAexpression of Bcl-2 in tumor tissues of high and low dose groups decreased significantly after drug administration, with a significantly lower level in high does group than that in low dose group (P<0.05). Conclusion: Ipilimumab can effectively inhibit TGF-β1/ERK signaling pathway, improve immune function and down-regulate the expression of Bcl-2, thus inhibit the growth of Lewis lung cancer cells and play an antitumor role in mice.