125 I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, survivin, livin and caspase-9 express
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RESEARCH
125
I seeds irradiation inhibits tumor growth and induces apoptosis by Ki‑67, P21, survivin, livin and caspase‑9 expression in lung carcinoma xenografts
Qing Jin2†, Cunzhi Lin1†, Xinhong Zhu3, Yiwei Cao1, Caihong Guo1 and Lijun Wang1*
Abstract Background: Lung cancer is a fatal disease and a serious health problem worldwide. Patients are usually diagnosed at an advanced stage, and the effectiveness of chemotherapy for such patients is very limited. Iodine 125 seed (125I) irradiation can be used as an important adjuvant treatment for lung carcinoma. The purpose of this study was to examine the role of irradiation by 125I seeds in human lung cancer xenograft model and to determine the underlying mechanisms involved, with a focus on apoptosis. Methods: 40 mice with A549 lung adenocarcinoma xenografts were randomly divided into 4 groups: control group (n = 10), sham seed (0 mCi) implant group (n = 10), 125I seed (0.6 mCi) implant group (n = 10) and 125I seed (0.8 mCi) implant group (n = 10), respectively. The body weight and tumor volume, were recorded every 4 days until the end of the study. Apoptotic cells were checked by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and activities of caspase-3 and caspase-8 enzyme were tested. Expression of P21, survivin, livin, caspase-9 and proliferating cell nuclear antigen (Ki-67) was detected with immunohistochemical staining. Results: The results of TUNEL staining assays showed that 125I seed irradiation suppresses the growth of lung cancer xenografts in nude mice and induced apoptosis. The activity of caspase-3 and caspase-8 was significantly higher. The expression levels Ki67, survivin and livin were substantially downregulated, while P21 and caspase-9 protein expression were significantly increased following 125I seed irradiation. This study revealed that 125I seed irradiation could significantly change apoptosis-related protein in human lung cancer xenografts. Conclusions: Overall, our study demonstrates that radiation exposure by 125I seeds could be a new treatment option for lung cancer. Keywords: 125I seeds, Lung carcinoma, Apoptosis, Ki-67, P21
*Correspondence: [email protected] † Qing Jin and Cunzhi Lin are the first authors and contributed equally to this work 1 Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China Full list of author information is available at the end of the article
Background Primary lung cancer is the most common malignancies [1] and the leading cause of tumor-associated mortality [2–8] in gender-independent populations. Approximately 1.8 million new cases are diagnosed and near 1.6 million fatal cases are estimated annually worldwide, accounting for 19.4% of total cancer mortality, and the 5-year overall survival rate is less than 20% [2, 5, 7, 9–12] Non-small cell lung cancer (NSCLC) accounts for approximately
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