Furthermore, the BI 2536 in vivo mitotic index and apoptotic index were assessed by quantitative morphometric analysis of PCNA expression and TUNEL, respectively. In our work, a declined mitotic index and increased apoptotic index were discerned in 125I treatment group compared with control group, which suggests that 125I seed irradiation can restrain tumor growth and lead to apoptosis Torin 1 supplier of cancer cells. Next, we use microarray gene expression profile analysis to study the mechanism of irradiation-mediated prevention of gastric tumors. To our knowledge, this is the first investigation to use microarray technology to study the role of 125I seed irradiation
in cancer treatment. At 28 days following 125I seed irradiation, the nude mice were sacrificed and gene expression was profiled in the xenografts by using gene expression microarrays. We found that the expression levels of 544 genes were significantly induced by 125I seed irradiation. Interestingly, among the irradiation-induced genes, many are involved in cell cycle, apoptosis
and cell division. The main pathways linked to these genes were further investigated by KEGG analysis and several apoptosis- or cell cycle-related pathways, such as MAPK and TGF-beta pathways, were clearly indentified. Then, the expression of 6 genes (BNIP3, MAPK8, BMF, RFWD3, CDKN2B and WNT9A), which were associated with apoptosis or cell cycle arrest, was further validated via real time PCR analysis Figure 3). BNIP3 (BCL2/adenovirus E1B 19 kDa interacting protein 3) is a proapoptotic member of the Bcl-2 family LOXO-101 concentration and its mutation and dysregulation might play a role in gastric carcinoma development . Recent study revealed that BNIP3 might play a role in enhancement of radiotherapy efficiency, and its expression might have a synergistic effect on radiation treatments . MAPK8 (Mitogen-activated protein kinase 8) is a member of the MAP kinase and JNK family. This gene is involved in UV radiation-induced apoptosis, which is thought to be related to
the cytochrome c-mediated cell death pathway . BMF (Bcl-2-modifying factor) is a Bcl-2 family member bearing only the BH3 domain and an essential inducer of apoptosis . BMF contributes to enhancing effects on apoptosis CYTH4 after ionizing radiation . RFWD3(ring finger and WD repeat domain 3) is an E3 ubiquitin ligase that positively regulates p53 levels and regulates G1 Checkpoint in Response to ionizing radiation . CDKN2B (Cyclin-dependent kinase 4 inhibitor B) belongs to a family of cyclin-dependent kinase 4 inhibitors (INK41) and controls cell proliferation during the G1 phase of the cell cycle . The expression of this gene was found to be dramatically induced by TGF beta, which suggested its role in the TGF beta induced growth inhibition . WNT9A is a member of the WNT gene family and over-expression of t human Wnt9a induced cell-cycle arrest at G1/S boundary .