These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Knockdown of TGF-β in Pancreatic Cancer Helps Ameliorate Gemcitabine Resistance.
    Author: Wang X, Su W, Qin C, Gao R, Shao S, Xu X, Zhang Z, Gao J.
    Journal: Front Biosci (Landmark Ed); 2024 Jul 25; 29(7):269. PubMed ID: 39082329.
    Abstract:
    BACKGROUND: The TGF-β gene is a gemcitabine (GEM) resistance gene; however, the mechanism by which it regulates GEM resistance in pancreatic cancer remains unclear. METHODS: The PANC-1 cell line was treated with GEM and then stimulated with TGF-β. Subsequently, we constructed GEM-resistant pancreatic cancer cell lines, knocked down TGF-β in these cell lines, and detected changes in the proliferation and apoptosis of drug-resistant cancer cells. In addition, the protein expression levels of KLF-4, GFI-1, and ZEB-1 were determined. The xenograft tumor models of nude mice were constructed by subcutaneously injecting GEM-resistant PANC-1 cells into mouse axilla. The tumors were removed, dissected, and weighed after 6 weeks. The protein levels of KLF-4, GFI-1, and ZEB-1 in tumor tissues were quantified. In addition, the percentage of M2 macrophages in tumor tissues was determined using flow cytometry. RESULTS: The protein levels of TGF-β in pancreatic cancer cells were significantly decreased after GEM treatment. The protein expression of KLF-4 was downregulated, whereas the expressions of GFI-1 and ZEB-1 were upregulated after TGF-β stimulation. Apoptosis increased and proliferation decreased after TGF-β knockdown in GEM-resistant pancreatic cancer cells, moreover, silencing TGF-β promoted the expression of Caspase 3 and Cleaved caspase 3. In addition, the protein expression of KLF-4 was upregulated, whereas the expressions of GFI-1 and ZEB-1 were downregulated. Further, the volume and weight of the transplanted tumor decreased after TGF-β knockdown. The protein expression of KLF-4 was upregulated, whereas the expressions of GFI-1 and ZEB-1 were downregulated in tumor tissues. In addition, the percentage of M2 macrophages decreased in tumor tissues after TGF-β knockdown. CONCLUSIONS: The knockdown of TGF-β inhibits epithelial-to-mesenchymal transition, suppresses the proliferation and promotes the apoptosis of drug-resistant cancer cells, and decreases the macrophage polarization to the M2 phenotype, consequently ameliorating GEM resistance in pancreatic cancer.
    [Abstract] [Full Text] [Related] [New Search]