[Therapeutic effect of brain-specific angiogenesis inhibitor 1 on glioblastoma: an animal experiment].

OBJECTIVE

To study the therapeutic effects of brain-specific angiogenesis inhibitor 1 (BAI1) on human glioblastoma and relevant mechanism.

METHODS

Recombinant adenovirus carrying human BAI1 cDNA, AdeBAI1 and recombinant adenovirus carrying LacZ, AdeMock, were constructed with the COS-TPC method. The successful construction of AdeBAI1 and expression of AdeBAI1 was verified using RT-PCR. Glioblastoma cells of the line U87MG were transplanted into the mice brain using stereotactic technique. AdeBAI1 and AdeMock were injected into the tumors after the tumors were developed. The survival of the mice was observed. Human glioblastoma cells of the lines SW1783, U87MG, and U373MG were cultured and transfected with AdeBAI1 or AdeMock, and then collected 48 hours later and counted using MTT method. The total RNA was extracted using Trizol agent. The mRNA of BAI1 and other angiogenesis related genes were detected using RT-PCR.

RESULTS

The mean survival time of the AdBAI1-treated mice was 26 +/- 4.6 d, significantly longer than that of the AdMock-treated mice (17.3 +/- 2.3 d, P < 0.05). RT-PCR showed that BAI1 mRNA was expressed only in the glioblastoma cells transfected with AdeBAI1. The number of AdeBAI1 treated glioblastoma cells was 2.12 +/- 0.18 x 10(5), significantly less than that of the AdeMock treated cells (4.23 +/- 0.18 x 10(5), P < 0.05). The mRNA expression of angiostatin of the AdeBAI1 treated cells was 0.66 +/- 0.08, significantly less than that of the AdMock-treated cells (0.95 +/- 0.12, P < 0.05). The mRNA expression of vascular endothelial growth factor (VEGF) of the AdeBAI1 treated cells was 0.68 +/- 0.07, significantly less than that of the AdMock-treated cells (1.02 +/- 0.14, P < 0.05). The mRNA expression of VEGF-B of the AdeBAI1 treated cells was 1.11 +/- 0.10, significantly more than that of the AdMock-treated cells (0.77 +/- 0.18, P < 0.05). The mRNA expression of thrombospondin of the AdeBAI1 treated cells was 1.16 +/- 0.16, significantly more than that of the AdMock-treated cells (0.60 +/- 0.22, P < 0.05).

CONCLUSION

Intratumor injection of AdeBAI1 can inhibit the tumor growth. The anti-tumor effect of BAI1 may arise from both anti-angiogenesis and anti-proliferation effects.