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125I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, survivin, livin and caspase-9 expression in lung carcinoma xenografts.

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.

SUBMITTER: Jin Q

PROVIDER: S-EPMC7559445 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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<sup>125</sup>I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, survivin, livin and caspase-9 expression in lung carcinoma xenografts.

Jin Qing Q Lin Cunzhi C Zhu Xinhong X Cao Yiwei Y Guo Caihong C Wang Lijun L

Radiation oncology (London, England) 20201015 1

<h4>Background</h4>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 (<sup>125</sup>I) 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, wi ...[more]

PMID: 33059701

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Project description:BACKGROUND: Iodine 125 (125I) seed irradiation can be used as an important supplementary treatment for unresectable advanced gastric cancer. Here, we aim to comprehensively elucidate the biological effects induced by 125I seed irradiation in human gastric cancer xenograft model by using global expression and DNA methylation analyses. METHODS: The 48 mice bearing NCI-N87 gastric cancer xenografts were randomly separated into 2 groups: sham seeds (O mCi) were implanted into the control group (n?=?24); 125?l seeds (0.9?mCi) were implanted into the treatment group (n?=?24). The mitotic index and apoptotic index were evaluated by quantitative morphometric analysis of the expression of proliferating cell nuclear antigen (PCNA) and in situ terminal transferase-mediated fluorescein deoxy- UTP nick end labeling (TUNEL), respectively. Global gene expression changes induced by 125I seed irradiation were analyzed by using Nimblegen Human gene expression array. DNA methylation profile in the tumors from control group was investigated with methylated DNA immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays. The changes in the methylation status of selected genes were further investigated by using MeDIP-PCR. RESULTS: 125I seed irradiation suppresses the growth of gastric cancer xenografts in nude mice. PCNA staining and tissue TUNEL assays showed that both inhibition of cell proliferation and induction of apoptosis contribute to the 125I-induced tumor suppression in nude mouse model. Gene expression profiles revealed that the expression levels of several hundred genes, many of which are associated with apoptosis or cell cycle arrest, including BMF, MAPK8, BNIP3, RFWD3, CDKN2B and WNT9A, were upregulated following 125I seed irradiation. Furthermore, the up-regulation of some of these genes, such as BNIP3 and WNT9A, was found to be associated with irradiation-induced DNA demethylation. CONCLUSIONS: This study revealed that 125I seed irradiation could significantly induce the up-regulation of apoptosis- and cell cycle-related genes in human gastric cancer xenografts. And some of the up-regulation might be attributed to 125I-irradiation induced demethylation in gene promoter regions. Collectively, these findings provided evidence for the efficacy of this modality for the treatment of gastric cancer.

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125I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, survivin, livin and caspase-9 expression in lung carcinoma xenografts.

Publications

<sup>125</sup>I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, survivin, livin and caspase-9 expression in lung carcinoma xenografts.

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