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Archive > Volume 23 Issue 2 > 2016,23(2):182-187. DOI:10.3872/j.issn.1007-385X.2016.02.005 Prev Next
Basic Research
Reversal effect of 4′-methylether-scutellarein on multidrug resistance of human choriocarcinoma
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Abstract:
Objective:To evaluate the reversal effect of 4′-methylether-scutellarein (4′-M-S) on multidrug resistance of human choriocarcinoma in vivo, and investigate its mechanism. Methods: Drug resistant human choriocarcinoma cells were subcutaneously injected into left armpits of BALB/c nude mice to construct the subcutaneous exnograft model. When diameter of the xenografts reached 1.0 cm, the mice were randomly divided into four groups with ten mice in each, namely control grop, etoposide (VP16) group, 4′-M-S group and 4′-M-S+VP16 group. After the treatment for three weeks, growths of the exnograft tumors were dynamically observed and survival times of the mice recorded in the various groups, morphological changes of the tumor tissues were observed with optical and transmission electron microscopes and apoptosis rates of the exnograft cells detected with flow cytometry assay. Expression levels of MDR1 mRNA, LRP mRNA and their coding proteins, P-gp and LR, were detected and compared among the four groups with RT-PCR and Western blotting assays respectively. Results: After the treatments for three weeks, it was found that 4′-M-S has somewhat inhibitory effect on drug-resistant human choriocarcinoma in vivo, 4′-M-S+VP16 could apparently inhibit growth of the exnograft tumors in the nude mice with inhibition rate of 48.21%. Meanwhile, toxicity of the chemotherapy was reduced, life quality of mice with the exnograft tumors obviously improved and their mean survival times significantly prolonged. In the 4′-M-S+VP16 group, apoptosis rate of the xenograft cells was significantly increased, and expression levels of MDR1 mRNA, LRP mRNA and their coding proteins, P-gp and LR, in the exnograft tumors significantly decreased comparing with the other three groups (all P<0.05) . Conclusion: 4′-M-S could effectively reverse resistance of the human choriocarcinoma to the chemotherapy drug VP16, which might be related with 4′-M-S inducing apoptosis of the tumor cells and down-regulating expression of MDR1 mRNA, LRP mRNA and their coding proteins, P-gp and LR, in the exnograft tumors.
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Project Supported:
Project supported by the Special Scientific Research from the Bureau of Educaton of Shaanxi Province (No. 12JK0768), and the Natural Science Foundation of Higher Education of Jiangsu Province (No. 06KJB360067)
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