MAPK/ERK Activation Sensitizes MKN-28 Cells to Cisplatin-Induced Apoptosis
DOI:
https://doi.org/10.17140/CSMMOJ-2-106Keywords:
Cisplatin, Gastric cancer, Apoptosis, ERK, BCL-2, BAKAbstract
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.
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