严 妍,王亚静,张 颐.低强度超声对卵巢癌SKOV3细胞增殖和凋亡的影响及机制分析[J].肿瘤学杂志,2024,30(1):38-50.
低强度超声对卵巢癌SKOV3细胞增殖和凋亡的影响及机制分析
Low-Intensity Ultrasound Inhibits Proliferation and Induces Apoptosis of Ovarian Cancer SKOV3 Cells and Its Mechanism
投稿时间:2023-09-03  
DOI:10.11735/j.issn.1671-170X.2024.01.B008
中文关键词:  卵巢癌  低强度超声  细胞凋亡  生物信息学
英文关键词:ovarian cancer  low intensity ultrasound  apoptosis  bioinformatics
基金项目:辽宁省应用基础研究计划(2022JH2/101300039);沈阳市科技计划(22-321-33-08);国家卫生健康委医药卫生科技发展研究中心(HDSL202003005)
作者单位
严 妍 中国医科大学附属第一医院 
王亚静 中国医科大学附属第一医院 
张 颐 中国医科大学附属第一医院 
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中文摘要:
      摘 要:[目的] 探讨低强度超声(low intensity ultrasound,LIUS)对于卵巢癌SKOV3细胞的促凋亡作用,并通过生物信息学分析其可能的作用机制。[方法] 通过细胞计数、CCK8实验及细胞凋亡测定证实LIUS对体外卵巢癌SKOV3细胞的促凋亡作用,并测定在不同照射强度及时间下细胞活力及细胞凋亡水平,筛选出最适的照射参数。通过现有的基因数据库获取可能被超声影响的潜在基因的表达谱,筛选差异基因进行KEGG富集分析及PPI网络构建。从现有癌症及预后数据库中提取关键基因的无进展生存期和总生存期数据进行预后分析,寻找LIUS促进卵巢癌细胞凋亡可能的机制。[结果] 随着LIUS照射时间及照射强度的增加,卵巢SKOV3细胞的贴壁数量及细胞活力明显降低,凋亡细胞数量增多,该作用呈时间及强度依赖性。在照射强度达到2.0 W/cm2,时间达到70 s时作用最强,此条件被认为是最佳照射参数。生物信息分析结果显示,LIUS可能通过上调YY1和HSPA5,下调GRN促进卵巢癌细胞凋亡。[结论] LIUS能够抑制卵巢癌SKOV3细胞增殖,诱导其凋亡,随着照射时间及强度的增加,细胞凋亡率增加。LIUS可能是由于上调YY1和HSPA5基因、同时下调GRN基因,协同促进卵巢癌细胞凋亡。
英文摘要:
      Abstract:[Objective] To investigate the effects of low-intensity ultrasound(LIUS) on proliferation and apoptosis of ovarian cancer cells and its mechanism. [Methods] Ovarian cancer SKOV3 cells were treated with LIUS, and the cell viability and apoptosis were determined by CCK8 assay and cytometry, respectively. The differentially expressed genes related to ultrasound treatment were obtained and screened with existing gene databases, and KEGG enrichment analysis and PPI network construction were performed. The progression free survival and overall survival associated with key gene expressions were extracted from existing cancer and prognostic databases for prognostic analysis, and the mechanisms of LIUS promoting apoptosis of ovarian cancer cells were analyzed. [Results] With the increase of LIUS irradiation time and intensity, the viability of SKOV3 cells decreased and the number of apoptotic cells increased significantly in a time and intensity dependent manner with an optimal intensity of 2.0 W/cm2 and optimal time of 70 s. The effect was strongest when the intensity reaches 2.0 W/cm2 and optimal time of 70 s, which was considered to be the best irradiation parameter. Bioinformatics analysis showed that LIUS may promote the apoptosis of ovarian cancer cells through up-regulating YY1 and HSPA5 genes and down-regulating GRN gene. [Conclusion] LIUS can inhibit the proliferation and induce apoptosis of ovarian cancer SKOV3 cells in a time and intensity dependent manner, which may be associated with up-regulation of YY1 and HSPA5 genes, and down-regulation of the GRN gene.
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