Roles of p38 and JNK protein kinase pathways activated by compound cantharidin capsules containing serum on proliferation inhibition and apoptosis of human gastric cancer cell line

Sun,Yonghao; Zhang,Dejuan; Mao,Mao; Lu,Yangping; Jiao,Ning

doi:10.3892/etm.2017.4704

Roles of p38 and JNK protein kinase pathways activated by compound cantharidin capsules containing serum on proliferation inhibition and apoptosis of human gastric cancer cell line

Authors:
- Yonghao Sun
- Dejuan Zhang
- Mao Mao
- Yangping Lu
- Ning Jiao
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Affiliations: Department of Internal Medicine, Zibo City Hospital of Traditional Chinese Medicine, Zibo, Shandong 255300, P.R. China, Clinical Medical Research Laboratory, Zibo City Hospital of Traditional Chinese Medicine, Zibo, Shandong 255300, P.R. China
Published online on: June 28, 2017 https://doi.org/10.3892/etm.2017.4704
Pages: 1809-1817

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Abstract

The aim of the present study was to investigate the inhibitory effect of compound cantharides capsules (CCCs) on the viability and apoptosis of human gastric cancer cell lines, BGC‑823 and SGC‑7901, and to detect its regulation of gene expression levels, as well as its inhibition mechanisms. Each cell line was grouped into a control group, CCC serum group, 5‑fluorouracil (5‑FU) group, combination therapy group (CCC serum + 5‑FU) and serum control group. Growth curves were measured and flow cytometry was used to detect cell apoptosis and cell viability. The mRNA expression level of proliferation‑related C‑MYC and p53 genes were assayed by reverse transcription‑quantitative polymerase chain reaction. Protein phosphorylation levels of proliferating cell nuclear antigen, p38 mitogen‑activated protein kinase, extracellular signal‑related kinase 1/2, c‑Jun N‑terminal kinase (JNK) and IκB were assayed by western blotting. The combined CCC serum and 5‑FU group exhibited a higher inhibition rate in both cell lines and CCC serum therapy demonstrated a similar effect to 5‑FU treatment, as demonstrated in the MTT and cell growth assay. Combined therapy significantly decreased the C‑MYC mRNA expression levels and increased p53 mRNA expression levels (P<0.05). Combined therapy of 5‑FU and CCC was more significant compared with CCC serum or 5‑FU only (P<0.05). P38 and JNK‑related protein phosphorylation are involved in apoptosis initiated by CCC combined 5‑FU therapy. Combined therapy was able to significantly inhibit human gastric cancer cell growth (P<0.05), and advance cell apoptosis compared with CCC serum only. CCC serum resulted in downregulation of the c‑Myc gene and upregulation of the p53 gene. p38 and JNK‑related protein phosphorylation is involved in the inhibition of cell viability and apoptosis of human gastric cancer cell lines.

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