Anticancer effects and mechanisms of Tanshinon ⅡA sulfonic acid on colon carcinoma cell line HT-29 transplanted subcutaneously in nude mice
AIM: To investigate the anticancer effects and the mechanism of Tanshinon HA sulfonic acid(TASA) on colon carcinoma cell line HT-29 transplanted subcutaneously in nude mice. METHODS: HT-29 human colon cancer cells were grown as xen-ografts in 24 immunodeficient mice,which were randomly divided into 4 groups. The mice in the observation groups were injected intraperitoneally with TASA at 1 mg/kg (low dosage),5 mg/kg (medium dosage) or 10 mg/kg (large dosage) respectively once per day for 2 weeks while the mice in the control group were injected with sodium chloride. All the nude mice were sacrificed 2 weeks later and growth inhibition rates of transplanted tumors were measured by weighing the masses. Apoptosis index was tested by TUNEL assay and microvascular density (MVD) was marked by CD34 staining. The protein expression levels of hypoxia-inducible factor 1 alpha ( HIF1 α),vascular endothelial growth factor (VEGF) and cyclooxygenase-2 ( COX2 ) were measured by immu-nohistochemistry. RESULTS: Compared with that in the control group,the apoptosis index significantly increased in the three observation groups (all P < 0.05 ). The medium dose TASA suppressed HT-29 cell proliferation and the growth inhibition rate was (26.0 ± 2.4) %. Compared with those in the control group,MVD and VEGF expressions were up-regulated in the observation groups,especially in the medium and large-dose groups (all P < 0.05). No significant difference was observed in the Cox-2 expression between the 4 groups. HIF1α expression was slightly but not significantly down-regulated in low-dose TASA group,while it was significantly up-regulated in the medium and large-dose groups as compared with that in the control group ( P < 0.05). CONCLUSION: Medium dosage of Tanshinon ⅡA sulfonic acid has some obvious anticancer effect of human colon carcinoma transplanted subcutaneously in nude mice. The probable mechanism may be related with the inducement of apoptosis and the up-regula-tion of hypoxia-inducible factor 1 alpha of human colon carcinoma.
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维普
