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10.1038/s41598-018-22250-8

http://scihub22266oqcxt.onion/10.1038/s41598-018-22250-8
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C5834501!5834501!29500444
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suck abstract from ncbi


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pmid29500444      Sci+Rep 2018 ; 8 (ä): ä
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  • Metformin-induced caveolin-1 expression promotes T-DM1 drug efficacy in breast cancer cells #MMPMID29500444
  • Chung YC; Chang CM; Wei WC; Chang TW; Chang KJ; Chao WT
  • Sci Rep 2018[]; 8 (ä): ä PMID29500444show ga
  • Trastuzumab emtansine (T-DM1) is an antibody drug conjugate (ADC) that was recently approved for the treatment of HER-2-positive metastatic breast cancer. The drug sensitivity of ADCs depends mainly on the internalization efficiency of the drug. Caveolin-1 was shown to promote T-DM1 internalization and enhance drug sensitivity. Whether caveolin-1 can be overexpressed to improve T-DM1 efficacy is interesting and has the potential for clinical application. In this study, diabetes drug metformin was investigated in terms of induction of caveolin-1 expression for increased efficacy of subsequent T-DM1 application. BT-474 cells were pretreated with metformin, followed by combined therapy with metformin and T-DM1. The T-DM1 internalization and drug efficacy were determined, and the protein expressions for signal transduction were also monitored. Caveolin-1 shRNA was applied to suppress endogenous caveolin-1 expression, and the ability of metformin to promote T-DM1 efficacy was investigated. Result showed that in BT-474 cells pretreated with metformin, cellular caveolin-1 overexpression was induced, which then promoted drug efficacy by enhancing T-DM1 internalization. As cellular caveolin-1 was suppressed by shRNA, the effect of metformin-enhanced T-DM1 cytotoxicity was decreased. This study demonstrated that metformin can be applied prior to T-DM1 treatment to improve the clinical efficacy of T-DM1 by enhancing caveolin-1-mediated endocytosis.
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