Volume 39 Issue 5
May  2023
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Article Navigation >  Journal of Nanjing University of traditional Chinese Medicine  > 2023  >  39(5): 474-482
LI Yu-xuan, LIU Chun-liang, YUAN Qin, CHEN Ting, JIANG Yan-tao, YAO Fei, SUN Hua, HAO Min-xia, ZHANG Lu-rong, LIU Min. Mechanism of Zhuidu Formula Regulating c-JUN, Inhibiting Abnormal Glycosylation, and Reversing Drug Resistance of Triple Negative Breast Cancer[J]. Journal of Nanjing University of traditional Chinese Medicine, 2023, 39(5): 474-482. doi: 10.14148/j.issn.1672-0482.2023.0474
Citation: LI Yu-xuan, LIU Chun-liang, YUAN Qin, CHEN Ting, JIANG Yan-tao, YAO Fei, SUN Hua, HAO Min-xia, ZHANG Lu-rong, LIU Min. Mechanism of Zhuidu Formula Regulating c-JUN, Inhibiting Abnormal Glycosylation, and Reversing Drug Resistance of Triple Negative Breast Cancer[J]. Journal of Nanjing University of traditional Chinese Medicine, 2023, 39(5): 474-482. doi: 10.14148/j.issn.1672-0482.2023.0474
shu

Mechanism of Zhuidu Formula Regulating c-JUN, Inhibiting Abnormal Glycosylation, and Reversing Drug Resistance of Triple Negative Breast Cancer

doi: 10.14148/j.issn.1672-0482.2023.0474
  • 1.

    Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215009, China

  • 2.

    The First Affiliated Hospital of Soochow University, Suzhou 215123, China

  • Received Date: 2022-10-11
    Available Online: 2023-05-19
    Abstract
  •   OBJECTIVE  To investigate the mechanism of reversal of drug resistance in triple negative breast cancer (TNBC) by Zhuidu Formula from the perspective of c-JUN-regulated glycosylation.  METHODS  MTT was used to detect cell proliferation. Western blot was used to detect the expression of c-JUN, β3GnT8, ppGalNAc-T1/2, CD147, and the drug resistance proteins BCRP and MDR1. MDA-MB-231/ADR cells overexpressing c-JUN were established using transfected c-JUN plasmids. In vivo experiments were performed by in situ transplantation of drug-resistant TNBC into nude mice.  RESULTS  Zhuidu Formula can significantly inhibit the proliferation of MDA-MB-231/ADR cells (P < 0.01), with a time-effect and dose-effect relationship. It also significantly inhibited the tumor weight of drug-resistant TNBC transplanted nude mice in situ (P < 0.01), reduced the expression of drug-resistant proteins BCRP and MDR1 (P < 0.01), and significantly decreased the expression of c-JUN, β3GnT8, ppGalNAc-T1/2, CD147 proteins (P < 0.01). After overexpression of c-JUN, the expression of β3GnT8, ppGalNAc T1/2, CD147, BCRP and MDR1 all showed an increase compared with the blank plasmid control group (P < 0.05, P < 0.01). The blank plasmid had no effect on the expression of the above proteins (compared with the blank control group, P > 0.05). Zhuidu Formula can significantly reduce the expression of the above proteins after overexpressing c-JUN, but the expression levels were still significantly higher than those in the blank plasmid group (P < 0.05, P < 0.01).  CONCLUSION  By acting on the regulatory factor c-JUN, Zhuidu Formula down-regulated the activation of β3GnT8 and ppGalNAc-T1/2, thereby inhibiting the glycosylation modification of CD147 and leading to the down-regulation of drug-resistant proteins BCRP and MDR1 to reverse TNBC drug resistance.

     

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