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

Zhan-Guo Zhang, Yan-Hui Wu, Hui-Fang Liang, Bi-Xiang Zhang and Wan-Guang Zhang*

MAPK/ERK Activation Sensitizes MKN-28 Cells to Cisplatin-Induced Apoptosis.
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 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. Transient transfection of MKN28 cells with Constitutively Active-MEK1 elevated cisplatin-induced apoptosis comparing with Dominant Negative-MEK. 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 ERK activation is required for the cisplatin-induced apoptosis in MKN-28 cells; and ERK mediates apoptosis by BCL-2. Cisplatin is a highly potent cytotoxic and genotoxic agent used in the chemotherapy for various types of cancers such as gastric cancer, which is one of the most malignant cancers in China. Apoptosis is an important pathogenic mechanism solidary tumor.

Cisplatin treatment in vivo and in vitro results in apoptosis of cancer cells, The primary mechanism of the cytotoxic effects is due to coordinative bonding between the atoms of platinum and DNA, leading to formation of intra-strand DNA cross-links, which induces apoptosis by activating p53 and cell cycle arrest.

Cancer Stud Mol Med Open J. 2015; 2(1): 52-59. doi: 10.17140/CSMMOJ-2-106