GROβ and its downstream effector EGR1 regulate cisplatin-induced apoptosis in WHCO1 cells

Cisplatin is one of the most widely used chemotherapeutic agents employed for treatment of a wide variety of solid tumors, including human esophageal squamous cell carcinoma (ESCC). However, a major limitation of cisplatin-based chemotherapy of ESCC is the rather low-effective rate. Understanding the molecular events of limited efficacy of cisplatin-based chemotherapy of ESCC could lead to strategies resulting in improved therapeutic benefits. The CXC chemokine family has been reported to be related to inflammatory reaction, injure recovery, cell proliferation, apoptosis and even to be involved in the regulation of chemotherapeutic agent-induced apoptosis. CXCL2 chemokine, also known as GRO beta (growth-related gene product beta), belongs to the CXC chemokine group. The known functions of GRO beta are related to attracting neutrophils to sites of inflammation, modulation of the neurotransmitter release, cell proliferation and apoptosis. However, little is known about the relationship between GRO beta and chemotherapeutic agent-induced apoptosis. This study was designed to provide insights into the possible role of GRO beta in the regulation of cisplatin-induced apoptosis in ESCCs. We report here that inhibition of expression of GRO beta can decrease cisplatin-induced apoptosis in WHCO1 cells. EGR1 is a downstream factor regulated by GRO beta. Silencing expression of EGR1 can also decrease cisplatin-induced apoptosis in WHCO1 cells. The activation of caspase 9 was delayed in cells in which GRO beta and EGR1 were knocked down after cisplatin treatment. All these results indicate that GRO beta and its downstream factor EGR1 are involved in regulating cisplatin-induced apoptosis in WHCO1 cells, and during this process the intrinsic apoptotic pathway is activated. It may be useful to examine the expression levels of GRO beta and EGR1 in ESCC patients to select those likely to respond well to cisplatin.