Tetrandrine combined with chemotherapeutic drugs induces reversal of multidrug resistance in zebrafish
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1.National&Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Guizhou Key Laboratory of Regenerative Medicine, Department of Pediatrics, Guizhou Medical University, Guiyang 550004, China. 2. Key Laboratory of Adult Stem Cell Translational Research, Chinese Academy of Medical Sciences, Guiyang 550004. 3. Department of Pediatrics, the Affiliated Hospital of Zunyi Medical University, Zunyi 563000. 4.Guiyang City Maternal and Child Health Center of Guizhou, Guiyang City Children’s Hospital, Guiyang 550003. 5. Guizhou University School,Guiyang 550025

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R-33

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    Abstract:

    Objective To investigate the effects of tetrandrine on early development in zebrafish embryos and the expression of multidrug resistance gene abcb4 and its mechanisms. Methods We used a drug toxicity test to analyze the mortality, hatching rate, heart rate, and deformity rate of zebrafish embryos treated with tetrandrine. Wild-type zebrafish embryos were divided into a blank control group, doxorubicin treatment group, vinblastine treatment group, tetrandrine treatment group, tetrandrine combined with doxorubicin treatment group, and tetrandrine combined with vinblastine treatment group. Drugs were administered to each group of embryos until the fifth day, and the embryos were then used for the experiment. Expression of the abcb4 gene was detected using real-time fluorescent quantitative PCR, and drug resistance was detected using the Rhodamine 123 test. Results Compared with the control group, low-dose tetrandrine had no teratogenic lethal effects on zebrafish embryos. High-dose tetrandrine significantly inhibited embryonic hatching rate and had clear lethal and teratogenic effects. Compared with the control group, the mRNA of the abcb4 gene increased when treated with doxorubicin and vinblastine alone, but decreased when exposed to tetrandrine combined with doxorubicin and vinblastine. The Rhodamine 123 experimental result showed evidence of drug resistance in zebrafish treated with doxorubicin and vinblastine alone, and indicated that tetrandrine combined with doxorubicin and vinblastine could reverse drug resistance. Conclusions Tetrandrine has low toxicity for zebrafish embryos early in development, and can reverse drug resistance to doxorubicin and vinblastine. These data suggest that tetrandrine may improve sensitivity to chemotherapy drugs and thus may enhance the therapeutic effect.

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History
  • Received:November 07,2019
  • Revised:
  • Adopted:
  • Online: June 19,2020
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