SLP-2 inhibits cisplatin-induced apoptosis through MEK/ERK signaling and mitochondrial apoptosis pathway in cervical cancer cells

Abstract

Stomatin-like protein 2 (STOML2 or SLP-2) is an oncogenic anti-apoptotic protein that is up-regulated in several types of cancer, including cervical cancer. However, the mechanisms responsible for the SLP-2 anti-apoptotic function remain poorly understood. Here, we show that siRNA-mediated SLP-2 suppression decreases growth of human cervical cancer HELA and SIHA cells, and increases cisplatin-induced apoptosis through activation of MEK/ERK signaling and suppression of the mitochondrial pathway. The inhibition of the mitochondrial pathway is mediated by increasing the mitochondrial Ca²⁺ concentration and mitochondrial membrane potential, thereby downregulating p-MEK and p-ERK levels, upregulating the Bax/Bcl-2 ratio, increasing cytochrome C release from mitochondria into the cytosol, and upregulating levels of cleaved-caspase 9, cleaved-caspase 3 and cleaved-PARP. SLP-2 overexpression using adenovirus-STOML2 has the opposite effect: it upregulates p-MEK and p-ERK and downregulates the Bax/Bcl-2 ratio and levels of cleaved-caspase 9 to caspase 9, cleaved-caspase 3 to caspase 3, and cleaved-PARP to PARP in cisplatin-treated cells. These data show that SLP-2 inhibits the cisplatin-induced apoptosis by activating the MEK/ERK signaling and inhibiting the mitochondrial apoptosis pathway in cervical cancer cells.

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