Study on Cantharidin Reversing the Drug-resistance of Non-small Cell Lung Cancer to DDP by Regulating the Expression of PD-L1

Abstract

Background and Purpose: Cantharidin can or cannot reverse the drug resistance of non-small cell lung cancer to cisplatin (DDP) by reducing the expression of programmed cell death ligand 1 (PD-L1).Materials and Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to screen for sublethal doses of cantharidin and determine its sensitizing effect on DDP. Detect the apoptosis rate of A549/DDP cells treated with cantharidin, DDP, or the combination of cantharidin and DDP. The effects of cantharidin on the expressions of p53 and PD-L1 in the cell line were investigated. Furthermore, pifithrin-α (PFT-α) pretreatment was performed to inhibit the function of p53 and verify whether cantharidin can affect the expression of PD-L1 through p53.Results: Cantharidin significantly enhanced the sensitivity of cells to DDP and increased the apoptosis of cells induced by DDP. Cantharidin upregulated the expression of p53 in A549/DDP cells with wild-type p53 and downregulated the expression of PD-L1. Pretreatment with PFT-α inhibited the apoptosis of cells induced by the combination treatment of cantharidin and DDP.Conclusion: Cantharidin can regulate the expression of p53 and downregulate the PD-L1 in non-small cell lung cancer with wild-type p53. It may enhance the sensitivity of non-small cell lung cancer to DDP by further altering the levels of PD-L1 through the regulation of p53 expression.

Keywords: Cantharidin; programmed cell death ligand 1; cisplatin