中国肿瘤生物治疗杂志2018，Vol.25Issue(10)：1026-1033,8.DOI:10.3872/j.issn.1007-385x.2018.10.009
小细胞肺癌组织显著低表达的SPIDR通过降低血清依赖促进NCI-H446细胞增殖
SPIDR significantly suppressed in tissues of small cell lung cancer promotes NCI-H446 cells proliferation by reducing serum dependence
摘要
Abstract
Objective: The present study was aimed to explore the role and distinctive mechanism of SPIDR, the key regulatory protein of homologous recombination pathway, in progression of small cell lung cancer (SCLC). Methods: 60 SCLC specimens and 44 normal lung tissues were collected from the patients undergoing tumor resection and bronchoscopic puncture in Shanghai Pulmonary Hospital Affiliated to Tongji University from January 2013 to January 2015. The expression of SPIDR in clinical samples and NCIH446 (SCLC cell line) and MRC-5 (normal cell line) were assayed by Real-time PCR. The role of SPIDR in SCLC was investigated in vivo and in vitro by the expression of SPIDR were artificially modified in NCI-H446. Results: Smoking was significantly associated with the occurrence of SCLC (P<0.01). The expression of SPIDR mRNA in SCLC tissues was lower than that of normal lung tissues (P<0.01), and the SPIDR transcriptional and translational levels of NCI-H446 cells were also lower than that of MRC-5. Although there is no significant changes of cell growth rate and susceptibility to cisplatin and etoposide in the NCI-H446 cells overexpressing SPIDR.However, the volume of xenograft tumors of overexpressed SPIDR group decreased by 58.99％ (P<0.01) and 61.84％ (P<0.01) than that of the original NCI-H446 cells and the NCI-H446 cells transfected with vector (pMSCV) and the average tumor mass decreased by61.70％ (P<0.01) and 70.25％ (P<0.01) respectively. When the fetal bovine serum content in the medium was reduced to 3％, the growth rate of NCI-H446 cells overexpressing SPIDR was 22.33％ (P<0.01) and 20.24％ (P<0.05) lower than that of the original NCIH446 cells and control group, the similar results were obtained from the 1％ serum concentration experiment as well. Conclusion: The expression of SPIDR, the key regulatory protein in the DNA double strand break homologous recombination repair pathway, was significantly suppressed in SCLC tissues, which markedly accelerated the growth of NCI-H446 cells in vivo and reduced the reliance of NCIH446 cells to the serum. The detailed mechanism is worthy of further investigation.关键词
小细胞肺癌/NCI-H446细胞/同源重组修复/SPIDR/血清依赖Key words
small cell lung cancer (SCLC)/NCI-H446 cell/homologous recombination repair/SPIDR/serum susceptibility分类
医药卫生引用本文复制引用
张泽忠,马伟,贾玉琳,其力格尔,方一,李春晖,厉建蕾,顾晔,邓子新,张海平..小细胞肺癌组织显著低表达的SPIDR通过降低血清依赖促进NCI-H446细胞增殖[J].中国肿瘤生物治疗杂志,2018,25(10):1026-1033,8.基金项目
国家自然科学基金委中日韩国际合作资助项目(No.21661140002) （No.21661140002）
