MAPK/ERK Activation Sensitizes MKN-28 Cells to Cisplatin-Induced Apoptosis

Abstract

Cisplatin as a highly potent cytotoxic agent was widely used in the chemotherapy of
gastric cancer. It kills cancer cells by inducing apoptosis. The Extracellular signal-regulated kinase
(ERK) signaling pathway plays an important role in proliferation and survival. However,
its roles in apoptosis vary. This study focused on the role of ERK in cisplatin-induced apoptosis
in a stomach cancer cell line, MKN-28 cells. We found that cisplatin treatment substantially activated
ERK, which was prevented by MEK inhibitor U0126. Transient transfection of MKN-
28 cells with Constitutively Active-MEK1 (CA-MEK1) elevated cisplatin-induced apoptosis
comparing with Dominant Negative-MEK1 (DN-MEK1). Cisplatin-induced ERK activation
up-regulates pro-apoptotic gene BAK, whereas down-regulates anti-apoptotic gene BCL-2.
Knocking down BCL-2 with siRNA sensitizes MKN-28 cells to the toxicity of cisplatin. These
results suggested that (1) ERK activation is required for the cisplatin-induced apoptosis in
MKN-28 cells; and (2) ERK mediates apoptosis by BCL-2.