Silencing of IGHG1 reverses the resistance of pancreatic cancer to multidrug chemotherapy by modulating autophagy
Background Pancreatic cancer is one of the most aggressive tumors with a high-mortality rate. First-line drugs include 5-fluorouracil (5-FU), gemcitabine (GEM), and oxaliplatin (OXA). Resistance to 5-FU, GEM, and OXA is a major challenge. Immunoglobulin heavy chain F1 (IGHG1) participates in the regulation of cancer progression. It is still unclear how IGHG1 affects 5-FU, GEM, and OXA in pancreatic cancer. Methods The expression status of IGHG1 in pancreatic cancer was analyzed through bioinformatics tools. IGHG1 expression in pancreatic cancer tissues and cells was determined via RT–qPCR. Cell counting kit 8 assays, and flow cytometry analysis were utilized to detect the impact of IGHG1,5-FU, GEM, and OXA on cell proliferation and apoptosis. Western blotting was utilized to detect changes in the levels of the autophagy-associated proteins LC3, Beclin-1, p62, and ATG5. Immunofluorescence assays were employed to determine LC3 expression in cells. Xenograft experiments were conducted on nude mice to study tumor growth. Results IGHG1 was overexpressed in pancreatic cancer cells and tissues. IGHG1 expression was downregulated by 5-FU, GEM, or OXA treatment in cells. Treatment with 5-FU, GEM, or OXA repressed viability and promoted apoptosis and autophagy in pancreatic cancer cells. IGHG1 silencing exhibited the same results. Furthermore, IGHG1 depletion notably strengthened the effects of 5-FU, GEM, and OXA on pancreatic cancer cell viability, apoptosis, and autophagy. The combination of IGHG1 depletion with 5-FU, GEM, or OXA significantly reduced tumor growth in vivo. Conclusion Silencing of IGHG1 could enhance 5-FU, GEM, or OXA function in pancreatic cancer and reverse resistance by regulating apoptosis and autophagy.
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