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Anti-gastrin vaccine mG17-CRM197 alone or in combination with 5-FU inhibits growth of mouse colon tumors
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Abstract:
Objective:To determine the inhibitory effect of anti-gastrin vaccine mG17-CRM197 (G17) alone or in combination with 5-FU on the growth of mouse transplanted C38 colon tumors. Methods: Gastrin receptor (CCKBR) expression in C38 cells was detected by Western blotting analysis, and the influence of G17 on proliferation of C38 cells was examined by sulforhodamine B（SRB）assay. C57BL/6 mice were randomly divided into 5 groups: PBS, CRM197, G17, 5-FU and G17/5-FU. The anti-G17 levels in mouse serum were measured by ELISA assay after immunization. After immunization, mice were subcutaneously injected with C38 cells, and then treated with 5-FU (20 mg/kg, q2d×5) in 5-FU and mG17/5-FU groups, or treated with 0.9% sodium chloride in the other groups. The influences of different therapies on the growth of C38-implanted tumors were evaluated by tumor growth-curves and tumor weights. Results: Mouse colon cancer C38 cells expressed CCKBR; mG17-NH2 dose-dependently increased the expression of CCKBR. Exogenous mG17-NH2 increased the proliferation of C38 cells, with the proliferation rate being 115.7%-133.5%. Mouse serum anti-G17 antibody was increased after immunization with G17 vaccine for 3 times. The tumor growth and tumor weights were significantly inhibited in G17, 5-FU and mG17/5-FU groups, with inhibitory rates being 58.0%, 60.5% and 80.7%, respectively (P<0.05), and tumor weight in mG17/5-FU group was less than those in the G17 and 5-FU groups. Conclusion：G17-CRM197 vaccine can inhibit the growth of mouse transplanted C38 colon tumors, and the inhibitory effect is enhanced when it is combined with 5-FU.
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Project Supported:
Project supported by the Major Scientific and Technological Special Project for “Significant New Drugs Creation” (No.2010ZX09401-302-2-25), and the Special Construction Engineering Foundation for “Taishan scholar” (No.200908)
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