TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression

Qing-Qing Liu; Feng-Feng Zhang; Fang Wang; Jing-Hua Qiu; Chun-Hua Luo; Guo-Yong Zhu; Ying-Fu Liu

doi:10.1371/journal.pone.0126176

TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression

PLoS One. 2015 May 6;10(5):e0126176. doi: 10.1371/journal.pone.0126176. eCollection 2015.

Authors

Qing-Qing Liu¹, Feng-Feng Zhang¹, Fang Wang², Jing-Hua Qiu¹, Chun-Hua Luo³, Guo-Yong Zhu⁴, Ying-Fu Liu¹

Affiliations

¹ Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, PR China.
² Department of Basic Medicine Science, NanYang Medical College, Nanyang, China.
³ The Department of Pathology, The Traditional Chinese Medical Hospital of Xiamen, Xiamen, Fujian, People's Republic of China.
⁴ Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, PR China.

Abstract

Recent studies found that TIPE2 was involved in cancer development. However, little is known about TIPE2 in lung cancer. Our study aims to clarify the role of TIPE2 in lung carcinogenesis. We examined the expression of TIPE2 in lung squamous cancer (LSC), small cell lung cancer and lung adenocarcinoma (AdC) tissues and found that TIPE2 expression was lost in small cell lung cancer, compared with adjacent non-tumor tissues. Overexpression of TIPE2 significantly inhibited the growth of lung cancer cell H446 in vitro and even suppressed tumor formation in vivo. Flow cytometry analysis found TIPE2 overexpression promoted apoptosis of H446. In TIPE2 over-expression cells, caspase-3, caspase-9, and Bax were significantly up-regulated while Bcl-2 was down-regulated. Moreover, coincident results were shown by immunohistochemistry in tumors from nude mice. TIPE2 inhibited the phosphorylation of Akt, while promoting the phosphorylation of P38, but had no effect on IκBα and ERK pathway. Taken together, TIPE2 promoted lung cancer cell apoptosis through affecting apoptosis-related molecules caspase-3, caspase-9, Bcl-2 and Bax, possibly via regulating P38 and Akt pathways, indicating that TIPE2 might be a novel marker for lung cancer diagnosis and therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / metabolism
Adenocarcinoma / pathology
Adenocarcinoma of Lung
Animals
Apoptosis / physiology*
Biomarkers, Tumor / metabolism
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology
Caspase 3 / metabolism
Caspase 9 / metabolism
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Heterografts
Humans
Immunohistochemistry
Intracellular Signaling Peptides and Proteins / deficiency
Intracellular Signaling Peptides and Proteins / metabolism*
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Small Cell Lung Carcinoma / metabolism
Small Cell Lung Carcinoma / pathology
Tumor Suppressor Proteins / metabolism
bcl-2-Associated X Protein / metabolism
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

BAX protein, human
BCL2 protein, human
Biomarkers, Tumor
Intracellular Signaling Peptides and Proteins
Proto-Oncogene Proteins c-bcl-2
TNFAIP8L2 protein, human
Tumor Suppressor Proteins
bcl-2-Associated X Protein
Proto-Oncogene Proteins c-akt
p38 Mitogen-Activated Protein Kinases
CASP3 protein, human
CASP9 protein, human
Caspase 3
Caspase 9

Grants and funding

Funding was provided by the National Natural Science Funds of China (81101764) http://www.nsfc.gov.cn/, the Natural Science Foundation of Fujian Province of China (2011J05099) http://www.fjkjt.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.