Abstract
BackgroundNumerous experimental and epidemiological studies have demonstrated a link between Clonorchis sinensis (C. sinensis) infestation and cholangiocarcinoma (CCA) as well as hepatocellular carcinoma (HCC). The underlying molecular mechanism involved in the malignancy of CCA and HCC has not yet been addressed. Csseverin, a component of the excretory/secretory products of C. sinensis (CsESPs), was confirmed to cause obvious apoptotic inhibition in the human HCC cell line PLC. However, the antiapoptotic mechanism is unclear. In the present study, we investigated the cellular features of the antiapoptotic mechanism upon transfection of the Csseverin gene.MethodsIn the present study, we evaluated the effects of Csseverin gene overexpression on the apoptosis of PLC cells using an Annexin PE/7-AAD assay. Western blotting was applied to quantify the activation of caspase-3 and caspase-9, the mitochondrial translocation of Bax and the release of Cyt c upon Csseverin overexpression in PLC cells. Laser scanning confocal microscopy was used to analyze the changes of intracellular calcium. Fluorescence assay and immunofluorescence assays were performed to observe the changes of the mitochondrial permeability transition pore (MPTP).ResultsThe overexpression of Csseverin in PLC cells showed apoptosis resistance after the induction of apoptosis. Additionally, the activation of caspase-3 and caspase-9 was specifically weakened in Csseverin overexpression PLC cells. The overexpression of Csseverin reduced the increase in intracellular free Ca2+, thereby inhibiting MPTP opening in PLC cells. Moreover, Bax mitochondrial translocation and the subsequent release of Cyt c were downregulated in apoptotic Csseverin overexpression PLC cells.ConclusionsThe present findings suggest that Csseverin, a component of CsESPs, confers protection from human HCC cell apoptosis via the inactivation of membranous Ca2+ channels. Csseverin might be involved in the process of HCC through C. sinensis infestation in affected patients.
Highlights
Clonorchis sinensis (C. sinensis) causes clonorchiasis, which is widely distributed in East Asia with heavily endemic zones in China, Taiwan, Vietnam, Russia, and Korea[1]
The present findings suggest that Csseverin, a component of CsESPs, confers protection from human hepatocellular carcinoma (HCC) cell apoptosis via the inactivation of membranous Ca2+ channels
Csseverin might be involved in the process of HCC through C. sinensis infestation in affected patients
Summary
Clonorchis sinensis (C. sinensis) causes clonorchiasis, which is widely distributed in East Asia with heavily endemic zones in China, Taiwan, Vietnam, Russia, and Korea[1]. In endemic areas of China, 16.44% of hepatocellular carcinoma (HCC) patients were infected with C. sinensis, while 2.40% of nontumor patients were infected [3]. This biocarcinogen has been included in control programs of neglected tropical diseases by the WHO[4]. The illumination of the precise mechanism linking C. sinensis with the development of HCC and CCA will help to prevent or postpone disease progression. Numerous experimental and epidemiological studies have demonstrated a link between Clonorchis sinensis (C. sinensis) infestation and cholangiocarcinoma (CCA) as well as hepatocellular carcinoma (HCC). A component of the excretory/secretory products of C. sinensis (CsESPs), was confirmed to cause obvious apoptotic inhibition in the human HCC cell line PLC. We investigated the cellular features of the antiapoptotic mechanism upon transfection of the Csseverin gene
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