Raised CD40L expression attenuates drug resistance in Adriamycin‑resistant THP‑1 cells

Abstract

Acute myeloid leukemia is a common hematological malignancy that often exhibits strong drug resistance when treated using conventional chemotherapy. Although numerous studies have been carried out to develop methods of overcoming drug resistance, the results have generally been unsatisfactory. CD40 ligand (CD40L) has been shown to improve the sensitivity of cancer cells to drug treatment. In the present study, Adriamycin (ADM)-resistant human monocytic THP-1 cells (THP-1/A cells) were developed by incubating THP-1 cells with increasing concentrations of ADM. Cells were transfected with CD40L vectors to explore the potential involvement of CD40L in regulating multidrug resistance (MDR) in cancer. Cell proliferation and viability were measured using the Cell Counting Kit-8 assay; cell apoptosis was evaluated by flow cytometry, trypan blue staining and caspase-3 activity; and the expression of MDR-associated protein 1 (MRP1) and permeability glycoprotein (P-gp) was analyzed using western blotting. The results revealed that the protein expression levels of MRP1 and P-gp were downregulated by raised CD40L expression and that the combination of raised CD40L expression with daunorubicin (DNR), a drug from which ADM is derived, significantly increased the extent of cell apoptosis, indicating that drug resistance was effectively attenuated by CD40L. Collectively, these results suggested that CD40L may contribute towards reducing DNR resistance in THP-1/A cells.

Soluble CD40 ligand inhibits the growth of non‑Hodgkin's lymphoma cells through the JNK signaling pathway

“…The suppression of CD40L expression in T cells has also been demonstrated in B cell chronic lymphocytic leukemia ( 14 ). Our previous study demonstrated that the upregulation of CD40L expression attenuated drug resistance in Adriamycin-resistant THP-1 cells ( 15 ). Furthermore, recent studies have demonstrated that CD40L may significantly inhibit the cell proliferation and promote the cell apoptosis of cancer cells, including colon cancer and ovarian cancer cells ( 16 , 17 ).…”