Study on the inhibitory effects and related toxicity of all-trans-retinoic acid combined with arsenic trioxide on transplanted tumor of human bladder neoplasms in nude mice / 中国医师杂志

ABSTRACT

ObjectiveTo investigate the inhibitory effects and related toxicity of all-trans-retinoic acid(ATRA) combined with arsenic trioxide(As2O3) on transplanted human bladder neoplasms in nude mice.MethodsThe subcutaneously transplanted tumor models of human bladder neoplasms in nude mice were established and then it was randomly divided into four teams: Saline group, ATRA group, As2 O3 group and the combination of ATRA and As2 O3 group.Each group composed of 10 nude mice and received intratumor injection in the following 14 d.The tumor growth inhibitory rate was calculated.The pathological changes of tumor,cardiac, liver, and kidney were observed after H.E.staining.The expression of MVD (Marked with CD43) and VEGF were detected by SP of immunohistochemistry.Blood routine examination and hepatic and nephritic functional examination was carried out to evaluate the side-effects.Results The tumor growth was significantly suppressed in ATRA group(inhibitory rate was 41.82％) and As2O3 group (inhibitory rate was 43.77％) compared with saline group.When ATRA combined with As2O3 ,inhibitory effects were improved(inhibitory rate was 68.55％).The difference of growth inhibitory rate between each group was obviously significant(x2 =26.81, P ＜0.01).There was less expression of MVD (Marked with CD43) and VEGF in ATRA group and As2 O3 group and the combination group compared with saline group (ODVEGF = 19.23 + 2.32,20.72 + 2.01,17.16 ± 1.59,27.33 ± 2.17, respectively; ODMVD = 44.77 + 8.25,43.39 + 7.41, 30.56 + 7.71,141.12 + 8.38, respectively), and the suppressed effect in the combination group was most significant (t = 3.16,3.08,3.37, P ＜ 0.01).WBC inhibition was seen in ATRA group and As2O3 group and the combination group, but no significantly difference among them(P ＞0.05).Hepatic and nephritic toxicity were not found.ConclusionsCombination of ATRA and .As2O3 had obvious synergistic effects on transplantéd tumor of human bladder neoplasm in nude mice, and moderate white blood cell inhibition and no hepatic or nephritic toxicity.