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目的:观察抗促胃液素(gastrin,又称胃泌素)疫苗mG17-CRM197(mG17)单用及联合氟尿嘧啶(fluorouracil,5-FU)对小鼠结肠癌C38移植瘤的抑制作用。方法:采用Western blotting法检测结肠癌细胞促胃液素受体(CCKBR)的表达情况,磺酰罗丹明B(SRB)法检测mG17-NH2对C38细胞增殖的影响。C57BL/6小鼠随机分为PBS组、CRM197组、mG17组、5-FU组和mG17/5-FU组,ELISA法检测小鼠血清中抗G17抗体水平;免疫后的小鼠皮下进行肿瘤移植,5-FU组和mG17/5-FU组给予5-FU(20 mg/kg,q2d×5),其他组给予生理盐水,通过肿瘤生长曲线和瘤质量评价不同治疗方案对C38移植瘤生长的影响。结果:小鼠结肠癌C38细胞表达CCKBR,mG17-NH2浓度依赖性上调CCKBR的表达,且能促进C38细胞增殖(细胞增殖率为115.7%~133.5%)。mG17疫苗免疫3次后,小鼠血清抗mG17抗体水平依次升高。mG17组、5-FU组和mG17/5-FU组对C38移植瘤有显著抑制作用,抑瘤率分别为58.0%、60.5%和80.7%;按金氏法计算,mG17与5-FU联用的Q值为0.97,两药联用出现相加作用。结论:mG17-CRM197疫苗对小鼠结肠癌C38移植瘤治疗有效,与5-FU联用增强对小鼠结肠癌的抑制。
OBJECTIVE: To observe the inhibitory effect of anti-gastrin vaccine mG17-CRM197 (mG17) combined with fluorouracil (5-FU) on mouse colon carcinoma C38 xenografts. Methods: The expression of gastrin receptor (CCKBR) in colon cancer cells was detected by Western blotting. The effect of mG17-NH2 on the proliferation of C38 cells was detected by SRB method. The C57BL / 6 mice were randomly divided into PBS group, CRM197 group, mG17 group, 5-FU group and mG17 / 5-FU group. The levels of anti-G17 antibody in sera of mice were detected by ELISA. , 5-FU (20 mg / kg, q2d × 5) were given to 5-FU group and mG17 / 5-FU group, and the other groups were given normal saline. The growth of C38 xenografts was evaluated by different tumor growth curves and tumor mass evaluation influences. Results: Colon cancer C38 cells expressed CCKBR in a concentration-dependent manner, while mG17-NH2 up-regulated the expression of CCKBR and promoted the proliferation of C38 cells (the cell proliferation rate was 115.7% -133.5%). MG17 vaccine immunized three times, the mouse serum anti-mG17 antibody levels in turn. The inhibitory rates of mG17, 5-FU and mG17 / 5-FU on C38 xenografts were 58.0%, 60.5% and 80.7%, respectively. According to King’s method, mG17 combined with 5-FU The Q value of 0.97, combined with the two drugs appear additive effect. CONCLUSION: The mG17-CRM197 vaccine is effective in the treatment of mouse colon cancer C38 xenografts and the combination with 5-FU enhances the inhibition of colon cancer in mice.