S100A8 promotes chemoresistance via augmenting autophagy in B-cell lymphoma cells

B-cell lymphomas (BCLs) are malignant lymphoid tumours originating from the malignant proliferation and transformation of mature lymphocytes at various stages of differentiation and clonal expansion of the lymphatic and circulatory systems. Efforts to control or even eradicate BCLs are frequently hampered by the development of drug resistance. Autophagy is an evolutionarily conserved biological process of the energy metabolism. By degrading intracellular organelles and proteins, autophagy provides cells with biochemical reaction substrates for the maintenance of homeostasis under nutrient deprivation or other stressful conditions. Accumulating evidence indicates that autophagy plays an important role in chemotherapy resistance. S100A8 is an important member of the calcium-binding protein family that plays an important role in regulating tumour resistance to chemotherapy, while the specific molecular regulatory mechanisms remain unclear. In the present study, by employing three BCL cell lines (Daudi, SUDHL-4 and JeKo-1), it was demonstrated that BCL cells with a strong drug resistance also exhibited active autophagy. In addition, S100A8 was found to be crucial for regulating drug resistance and promoting autophagy in BCL cells. Interference of S100A8 significantly downregulated Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 located in the mitochondria and endoplasmic reticulum to further inhibit autophagy. In addition, S100A8 interference markedly inhibited the formation of the BECN1-PI3KC3 complex and promoted B-cell lymphoma 2 expression, which collectively inhibited autophagy.