Efficacy of intratumoral chemotherapy using arsenic trioxide (As2O3) sustained release tablets for the treatment of neurogliocytoma in nude mice

H.-B. Zhao, Q.-X. Sun, X.-F. Chen, D.-Y. Han, S.-G. Zhao

Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China. shiguangzhaocn@163.com

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• Oncology

OBJECTIVE: This study aimed to investigate the inhibiting effect of arsenic trioxide (As2O3) on neurogliocytoma in nude mice and the mechanism responsible for this effect.

MATERIALS AND METHODS: Neurogliocytoma implantation models were constructed in nude mice, which were assigned to three groups: the control group, the sustained release tablet-polylactic acid-glycolic acid polymer (50:50) group (PLGA group) and the As2O3-polylactic acid-glycolic acid polymer (50:50) (As2O3-PLGA group). One tablet of As2O3-PLGA was implanted in the tumor of the As2O3-PLGA group. Intratumoral implantation was also performed in the other groups using a different type of tablet. The sustained releasing As2O3 had an inhibiting effect on the tumors. The TUNEL assay was used to determine the apoptosis rates in the implanted tumors. Immunohistochemical staining and Western blotting was carried out to determine the expression levels of caspase-3 and Bcl-2.

RESULTS: No inhibitory effect was observed on the tumor in the PLGA group, and there was no significant difference between this group and the control group. Subcutaneous tumor growth in nude mice was significantly inhibited in the As2O3-PLGA group relative to that in the control group, and the difference was statistically significant (p < 0.01). The tumor inhibition rate was 60.8%. The percentage of apoptotic tumor cells in the As2O3-PLGA group was 30.8%, which was significantly higher than that in the control group (3.92%) and that in the PLGA group (4.08%). The expression of Bcl-2 in the implanted tumor tissue was significantly reduced, but the expression of caspase-3 increased significantly.

CONCLUSIONS: As2O3 has a potent inhibiting effect on the growth of neurogliocytoma in vivo and can induce the apoptosis of tumor cells. The molecular mechanism of this effect may be related to the downregulation of Bcl-2 expression and the upregulation of caspase-3 expression.

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