摘要
目的 探讨IFI6调控舌鳞癌顺铂耐药性和抗肿瘤的作用机制。方法 临床样本分析探索IFI6表达量与舌鳞癌患者顺铂化疗耐药、临床病理特征以及预后的关系;通过沉默和过表达舌鳞癌细胞系中IFI6表达水平,明确IFI6对舌鳞癌细胞顺铂耐药和迁移侵袭能力的影响,采用免疫荧光和激光共聚焦显微镜检测,明确IFI6在细胞中的定位,采用蛋白免疫印迹法(Westernblot,WB)检测IFI6表达水平与线粒体依赖性凋亡途径中主要靶基因Caspase3和Caspase9蛋白表达水平的关系。结果 127例舌鳞癌患者石蜡标本免疫组化分析发现,舌鳞癌组织中IFI6表达量明显高于癌旁组织(P<0.05),其中化疗耐受肿瘤组织中的表达量显著高于化疗敏感肿瘤组织(P<0.05);同时对临床随访资料进行初步生存曲线分析,结果显示IFI6高表达的患者,其预后较差(P<0.05)。CAL27-re沉默IFI6后,降低了细胞的迁移、增殖、侵袭能力;CAL27过表达IFI6后,增强了舌鳞癌细胞的顺铂耐药性和迁移、增殖、侵袭能力。使用激光共聚焦显微镜观测,发现IFI6主要定位于线粒体中;在舌鳞癌CAL27与其顺铂耐药株CAL27-re中,分别过表达和沉默IFI6,通过WB检测发现IFI6表达量与Caspase3/9的活性呈正相关。结论 IFI6可能通过增强线粒体膜稳定性,负性调控凋亡蛋白活性,从而起到抗肿瘤凋亡作用,提高舌鳞癌顺铂耐药性和迁移侵袭能力。
Objective To explore the mechanism by which IFI6 regulates cisplatin resistance and its anti-tumor effects in tongue squamous cell carcinoma(TSCC).Methodss Clinical sample analysis was performed to investigate the relationship between IFI6 expression and cisplatin resistance,clinicopathological characteristics,and prognosis in TSCC patients.The expression levels of IFI6 in TSCC cell lines were silenced and overexpressed to determine its effect on cisplatin resistance,migration,and invasion abilities of TSCC cells.Immunofluorescence and laser confocal microscopy were used to detect IFI6 localization within cells.Western blot(WB)was utilized to examine the relationship between IFI6 expression and the expression of key target genes Caspase3 and Caspase9 involved in the mitochondrial-dependent apoptosis pathway.Results IFI6 expression was significantly higher in TSCC tissues compared to adjacent non-tumor tissues,with even higher expression in chemotherapy-resistant tumors compared to chemotherapy-sensitive tumors.Preliminary survival curve analysis of clinical follow-up data indicated that high IFl6 expression was associated with poor prognosis(P<0.05).Silencing IFI6 enhanced cisplatin sensitivity,reduced cell migration,proliferation,and invasion abilities.Conversely,overexpressing IFI6 increased cisplatin resistance and enhanced migration,proliferation,and invasion capabilities of TSCC cells.Laser confocal microscopy revealed that IFI6 was primarily located in mitochondria.In the TSCC cell line CAL27 and its cisplatin-resistant subline CAL27-re,overexpression and silencing of IFI6 demonstrated a positive correlation between IFI6 expression and Caspase3/9 activity by WB analysis.Conclusion IFI6 may enhance mitochondrial membrane stability and negatively regulate the activity of apoptosis-related proteins,thereby exerting anti-apoptotic effects,promoting cisplatin resistance,and enhancing migration and invasion abilities of TSCC cells.
作者
程慧琳
夏昕
黄卓珊
CHENG Hui-lin;XIA Xin;HUANG Zhuo-shan(Department of Stomatology,Sun Yat-Sen Memorial Hospital,Sun Yat-Ssen Unirersity,Guangzhou 510160,Guangdong,China)
出处
《广东医学》
2025年第5期659-665,共7页
Guangdong Medical Journal
基金
广东省自然科学基金面上项目(2022A1515010187)。
关键词
IFI6
舌鳞癌
顺铂耐药
线粒体
IFI6
tongue squamous cell carcinoma
cisplatin resistance
mitochondria
