Open AccessStomatin‐like protein 2 inhibits cisplatin‐induced apoptosis through MEK/ERK signaling and the mitochondrial apoptosis pathway in cervical cancer cells
Author(s) -
Hu Guolin,
Zhang Jialu,
Xu Feifei,
Deng Huan,
Zhang Weiwei,
Kang Shijun,
Liang Weijiang
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13563
Subject(s) - apoptosis , cytochrome c , mapk/erk pathway , poly adp ribose polymerase , hela , cisplatin , microbiology and biotechnology , mitochondrion , cancer cell , chemistry , signal transduction , caspase , downregulation and upregulation , cancer research , biology , cancer , programmed cell death , cell , biochemistry , polymerase , dna , genetics , chemotherapy , gene
Stomatin‐like protein 2 ( STOML 2 or SLP ‐2) is an oncogenic anti‐apoptotic protein that is upregulated 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 si RNA ‐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 Ca 2+ 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 poly ADP‐ribose polymerase (PARP). Overexpression of SLP ‐2 using adenovirus‐ STOML 2 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 cisplatin‐induced apoptosis by activating the MEK / ERK signaling and inhibiting the mitochondrial apoptosis pathway in cervical cancer cells.