Anti-tumor effect and its mechanism of co-administration of fusion proteins hVEGF121/βhCG and mGM-CSF/βhCG

JING Liangliang; MIAO Zitao; LI Manman; YE Jia; JIN Liang; CAO Rongyue; LONG Jun

doi:10.11665/j.issn.1000-5048.20170116

Journal of China Pharmaceutical University > 2017 > 48(1): 102-109. > DOI: 10.11665/j.issn.1000-5048.20170116

JING Liangliang, MIAO Zitao, LI Manman, YE Jia, JIN Liang, CAO Rongyue, LONG Jun. Anti-tumor effect and its mechanism of co-administration of fusion proteins hVEGF121/βhCG and mGM-CSF/βhCG[J]. Journal of China Pharmaceutical University, 2017, 48(1): 102-109. DOI: 10.11665/j.issn.1000-5048.20170116

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Anti-tumor effect and its mechanism of co-administration of fusion proteins hVEGF121/βhCG and mGM-CSF/βhCG

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This study aimed at investigating the inhibitory effects and the anti-tumor mechanisms of co-administration of fusion proteins mGM-CSF/βhCG(GC)and hVEGF121/βhCG(VC)on RM-1 prostatic cancer and B16F10 melanoma in the C57BL/6J mouse model. Two recombinant stains containing pET-28a-mGM-CSF-X10-βhCGCTP37 and pET-28a-VEGF-M2-X10-βhCG-CTP37 were induced by lactose to express fusion proteins. The fusion proteins were separated and purified to prepare the anti-tumor protein vaccines(VC protein vaccine and GC protein vaccine), which were then mixed to prepare a combined protein vaccine named VGC protein vaccine. The prostatic cancer and melanoma tumor-bearing mice C57BL/6J were immunized with described vaccines, then the growth of each tumor was measured; splenocyte proliferation of immunized mice was detected; and the cytotoxic effects of the vaccine on tumor cells were tested. After that, the in vivo concentrations of IFN-γ and anti-hVEGF antibodies were investigated by ELISA. The difference between each experimental group and normal saline group(NS)was statistically significant in both tumor-bearing mouse models(P< 0. 05)respectively. Besides, VGC group exhibited significantly better anti-tumor effect compared with the GC and VC groups with the anti-tumor rate(41. 7±0. 83)% and(46. 4±1. 27)% for prostatic cancer and melanoma tumor, respectively. The co-administration of the two proteins, VC and GC, could inhibit the growth of RM-1 prostatic tumor and B16F10 melanoma effectively via anti-tumor immunity and anti-tumor angiogenesis.

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Anti-tumor effect and its mechanism of co-administration of fusion proteins hVEGF121/βhCG and mGM-CSF/βhCG

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