Expression of programmed cell death 5 protein inhibits progression of lung carcinoma in vitro and in vivo via the mitochondrial apoptotic pathway.

Abstract

Lung cancer is one of the most common and serious types of cancer, and is characterized by uncontrolled cell growth and metastasis from lung tissues to other body parts. The programmed cell death 5 (Pdcd5) protein is known to accelerate apoptosis in different cell types of tumor. The aim of the present study was to explore the role of Pdcd5 in lung carcinoma and to identify the mechanisms underlying the antitumorigenic properties of Pdcd5 in lung cancer. First, we detected and compared the expression of Pdcd5 in healthy and highly differentiated adenocarcinoma lung tissues. The results of histochemical staining and western blot analysis demonstrated that Pdcd5 expression is markedly decreased in highly differentiated lung adenocarcinoma. Next, we used the lung adenocarcinoma cell line A549 to study the effects of Pdc5 expression on proliferation and colony formation. The results revealed that the expression of Pdcd5 significantly inhibits cell proliferation and colony formation in A549 cells. Importantly, Pdcd5 expression induced tumor cell apoptosis, and the apoptotic proteins caspase-3 and -9 were activated. The expression of B-cell lymphoma 2 (Bcl-2) was reduced and that of Bcl2‑associated X protein (Bax) was increased, overall suggesting that the intrinsic apoptotic pathway is activated. Furthermore, using a mice xenograft model and vectors for stable expression or silencing of Pdcd5, we showed that stable expression of the protein significantly increases the survival rate of mice in vivo (P<0.01 compared to control). In conclusion, both in vitro and in vivo experiments demonstrated that Pdcd5 expression inhibits proliferation and induces apoptosis in the A549 cell line, indicating that the Pdcd5 protein may play an important role in the progression of lung cancer. Therefore, Pdcd5 may be a promising target for the therapy of lung carcinoma.

• Authors: Shining Xu, Gang Sui, Lei Yuan, Zhiqiang Zou
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 10 Issue 4 Pg. 2059-64 (Oct 2014) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25109624 (Publication Type: Journal Article)

Chemical References

• Apoptosis Regulatory Proteins
• Neoplasm Proteins
• Pdcd5 protein, mouse
• Proto-Oncogene Proteins c-bcl-2
• RNA, Small Interfering
• bcl-2-Associated X Protein
• Caspase 3
• Caspase 9

Topics

• Adenocarcinoma (metabolism, mortality, pathology)
• Animals
• Apoptosis
• Apoptosis Regulatory Proteins (antagonists & inhibitors, genetics, metabolism)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cell Line, Tumor
• Humans
• Lung Neoplasms (metabolism, mortality, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mitochondria (metabolism)
• Neoplasm Proteins (antagonists & inhibitors, genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Survival Rate
• Transplantation, Heterologous
• bcl-2-Associated X Protein (metabolism)