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目的:研究重组鼠Muc1-MBP蛋白的体内抗肿瘤作用.方法:采用皮下注射法将不同剂量Muc1-MBP蛋白免疫小鼠,2wk/次,共免疫3次.在第3次免疫后4d,给予C57BL/6小鼠尾静脉注射LLC1细胞,或给予5GyX射线照射的ICR小鼠背部皮下注射MCF-7细胞.注射3wk后剥离并测量肿瘤大小;肿瘤组织行常规HE染色.免疫组织化学染色分析肿瘤周围浸润的淋巴细胞亚群.结果:LLC1细胞尾静脉接种后21d,肺肿瘤结节对照组,Muc1-MBP0.15g/L组小鼠分别为54和39个(100%),Muc1-MBP0.3g/L组小鼠共计17个(60%),提示Muc1-MBP0.3g/L组可显著抑制肺癌的生长(P<0.05),Muc1-MBP0.15g/L组作用较弱.皮下接种MCF-7细胞后21d,对照组,Muc1-MBP0.15g/L组小鼠100%(6/6)可见乳腺癌瘤体形成,平均体积分别为(142.8±70.2)和(96.1±53.4)mm3,Muc1-MBP0.3g/L组瘤体形成66.7%(4/6),平均体积为(54.5±46.7)mm3.表明Muc1-MBP0.3g/L组免疫后可显著抑制人乳腺癌移植瘤生长(P<0.05),Muc1-MBP0.15g/L组作用较弱.免疫组化结果显示Muc1-MBP免疫组肿瘤周围有大量CD4+和CD8+T的细胞浸润到肿瘤周围.结论:Muc1-MBP诱导免疫能够明显抑制LLC1,MCF-7细胞的生长,为临床应用研究奠定了基础.
OBJECTIVE: To study the anti-tumor effect of recombinant mucin-MBP protein in vivo. Methods: The mice were immunized with different doses of Muc1-MBP protein by subcutaneous injection for 2 weeks, and were immunized three times. Four days after the third immunization, the mice were given C57BL/6 mice were injected with LLC1 cells via tail vein, or MCF-7 cells were injected subcutaneously into the back of ICR mice irradiated with 5 Gy X-rays. After 3 weeks of injection, the tumors were detached and the tumor size was measured. The tumor tissues were routinely stained with HE. Immunohistochemical staining was used to analyze tumors. Peripheral infiltrating lymphocyte subsets. Results: 21 days after tail vein inoculation of LLC1 cells, lung tumor nodules in the control group, Muc1-MBP 0.15g/L mice were 54 and 39 (100%), Muc1-MBP0. A total of 17 mice (60%) in the 3 g/L group showed that the Muc1-MBP 0.3 g/L group significantly inhibited the growth of lung cancer (P<0.05), and the Muc1-MBP 0.15 g/L group had a weaker effect. At 21 days after -7 cells, 100% (6/6) mice in the control group, Muc1-MBP 0.15g/L group showed breast tumor formation with an average volume of (142.8±70.2) and (96.1±53.4) mm3, respectively. In the Muc1-MBP0.3g/L group, the tumor formation was 66.7%(4/6) with an average volume of(54.5±46.7)mm3. This indicated that the Muc1-MBP0.3g/L group could significantly inhibit the growth of human breast cancer after immunization ( P<0.05), Muc1-MBP 0.15 g/L group The effect was weak. Immunohistochemistry results showed that a large number of CD4+ and CD8+T cells infiltrated around the tumor in the Muc1-MBP-immunized group. Conclusion: Muc1-MBP-induced immunity can significantly inhibit the growth of LLC1 and MCF-7 cells. Clinical application studies laid the foundation.