Silibinin induces G1 arrest, apoptosis and JNK/SAPK upregulation in SW1990 human pancreatic cancer cells

Zhang,Xiaokai; Liu,Jiming; Zhang,Peng; Dai,Liting; Wu,Zhihui; Wang,Li; Cao,Mingrong; Jiang,Jianwei

doi:10.3892/ol.2018.8541

Silibinin induces G1 arrest, apoptosis and JNK/SAPK upregulation in SW1990 human pancreatic cancer cells

Authors:
- Xiaokai Zhang
- Jiming Liu
- Peng Zhang
- Liting Dai
- Zhihui Wu
- Li Wang
- Mingrong Cao
- Jianwei Jiang
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Affiliations: Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Biochemistry, Medical College, Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Laboratory, Panyu Center Hospital, Guangzhou, Guangdong 511400, P.R. China
Published online on: April 19, 2018 https://doi.org/10.3892/ol.2018.8541
Pages: 9868-9876
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the inhibitory effect of silibinin on SW1990 pancreatic cancer cells. An MTT assay following silibinin treatment demonstrated an inhibitory effect on AsPC‑1 and SW1990 cells in a dose‑ and time‑dependent manner. Propidium iodide staining analysis identified the cell cycle arrest of G1 phase and western blotting analysis demonstrated that the expression levels of cyclin D1, cyclin E2, cyclin A and cyclin B1 were decreased. The expression of G1‑associated cell cycle‑dependent kinases, cyclin‑dependent kinase (CDK)4 and CDK6, were also decreased, whereas the expression of p15 (p15INK4B) was increased. In addition, after SW1990 cells were incubated with various concentrations of silibinin, early and late apoptotic cells were detected using flow cytometry. Silibinin increased the activities of caspase‑9 and caspase‑3, and subsequent cleavage of poly (ADP‑ribose) polymerase (PARP) was also observed. The expression levels of B‑cell lymphoma (Bcl)‑2, Bcl‑2‑like 1 and myeloid cell leukemia 1 were decreased, whereas the expression of Bcl‑like protein 4 did not alter and the expression levels of Bcl‑2‑like 1 small and Bcl‑2‑like protein 11 were increased. The expression levels of c‑Jun N‑terminal kinase (JNK) and phospho‑JNK were also increased. In conclusion, silibinin inhibited cell proliferation, induced cell cycle G1 arrest via upregulating p15INK4B and induced mitochondrial apoptosis via upregulating JNK/stress‑activated protein kinase (SAPK) signaling pathway in human pancreatic cancer SW1990 cells.

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