Low-doses of aspirin promote the growth of human PC-9 lung cancer cells through activation of the MAPK family.

Abstract

Aspirin has been reported for its anti-tumor activity, however, there are few studies on its effects in lung cancer. The present study found that aspirin had a dual role in the proliferation of human lung cancer PC-9 (formerly known as PC-14) and A549 cells, and in human colon cancer HCT116 cells. The cells were treated with 0, 1, 2, 4, 8 and 16 mM aspirin for 24-72 h or 7-12 days and cell proliferation was examined by MTT and colony formation assay. In order to explore the relationship between the proliferation-enhancing effect of low-dose aspirin and mitogen-activated protein kinase (MAPK) signaling activation, PC-9 cells were pretreated with 10 µM PD98059 (a specific inhibitor of ERK), SB203580 (a specific inhibitor of p38) and SP600125 (a specific inhibitor of JNK) for 30 min respectively. Western blot assay was performed to detect the activation of MAPK members in PC-9 cells. Cellular apoptosis was detected using flow cytometer-based Annexin V/propidium iodide dual staining. An assessment of MAPK inhibitors was performed to further validate the role of JNK, p38 and ERK in aspirin-promoted PC-9 cell growth. It was demonstrated that aspirin could promote the growth of human PC-9 lung cancer cells and induced MAPK activation at low concentrations. All the MAPK inhibitors tested (PD98059, SB203580 and SP600125) were able to inhibit the aspirin-induced proliferation of PC-9 cells.