热疗联合化疗下调HIF-1α、CYPJ的表达诱导舌鳞癌细胞凋亡  

Hyperthermia combined with chemotherapy induce tongue squamous cell carcinoma cell apoptosis by down-regulating HIF-1αand CYPJ expression

作　　者：石凡 孙巧珍 周学筱 徐婷[2] 宋轶鹏[3] 王升志[2] Shi Fan;Sun Qiaozhen;Zhou Xuexiao;Xu Ting;Song Yipeng;Wang Shengzhi(School of Stomatology,Qingdao University,Qingdao 266003,China;Department of Oral and Maxillofacial Surgery,Yantai Yuhuangding Hospital Affiliated to Qingdao University,Yantai 266400,China;Department of Radiotherapy,Yantai Yuhuangding Hospital Affiliated to Qingdao University,Yantai 266400,China)

机构地区：[1]青岛大学口腔医学院,266003 [2]青岛大学附属烟台毓璜顶医院口腔颌面外科,266400 [3]青岛大学附属烟台毓璜顶医院放疗科,266400

出　　处：《中华放射肿瘤学杂志》2021年第3期283-288,共6页Chinese Journal of Radiation Oncology

摘　　要：目的探讨HIF-1α、CYPJ在舌鳞癌细胞(TSCC)中的作用及意义,并进一步研究热疗对HIF-1α、CYPJ的调控作用。方法收集TSCC患者癌组织及癌旁正常组织标本80例,采用免疫组化、蛋白印迹、荧光定量PCR检测各标本中HIF-1α、CYPJ的表达及其与临床病理特征之间的关系。采用qPCR、蛋白印迹检测Cal-27细胞在常氧及乏氧状态下以及用42℃热疗、化疗及热化疗处理时HIF-1α、CYPJ的表达情况。细胞划痕检测细胞迁移,流式细胞术检测细胞凋亡。结果HIF-1α、CYPJ蛋白在TSCC患者肿瘤组织中的表达水平高于相应的癌旁组织;且二者表达升高与TSCC患者肿瘤大小、TNM分期、分化程度、淋巴结转移等相关(均P<0.05),与性别、年龄无关(均P>0.05)。Cal-27细胞中HIF-1α、CYPJ表达水平在乏氧微环境中升高(均P<0.05),且单独热疗也促进其表达(均P<0.05)。相比于单独热疗及化疗,热化疗联合使用在明显抑制二者的表达的同时抑制细胞迁移并促进细胞凋亡(均P<0.05)。结论HIF-1α、CYPJ是TSCC肿瘤发生和预后的一个潜在生物标志物,且热疗后肿瘤复发可能源于热疗触发了HIF-1α表达,其通过激活下游靶基因促使适应热处理的肿瘤细胞生长存活,而热疗联合化疗可能是治疗TSCC一种比较有前景的治疗方案。Objective The investigate the roles and significance of HIF-1αand CYPJ in tongue squamous cell carcinoma cell(TSCC),and further evaluate the regulatory effect of hyperthermia(HT)on HIF-1αand CYPJ in TSCC cells.Methods Eighty samples of cancer tissues and adjacent normal tissues from TSCC patients were collected.The expression levels of HIF-1αand CYPJ were detected by immunohistochemistry,Western blotting(WB)and fluorescence quantitative PCR,and the relationship between the expression levels of HIF-1αand CYPJ and clinicopathological characteristics was further analyzed.The expression levels of HIF-1αand CYPJ in Cal-27 cells under normoxic and hypoxic conditions for 24 h when combined with HT(42℃),chemotherapy and both were detected by qPCR and WB.Cell migration was detected by cell scratch test and cell apoptosis was measured by flow cytometry.Results The expression levels of HIF-1αand CYPJ proteins in the tumor tissues of TSCC patients were higher than those in the adjacent normal tissues,which were significantly correlated with tumor size,TNM stage,differentiation degree and lymph node metastasis in TSCC patients(all P<0.05),whereas they were not correlated with gender or age(all P>0.05).The expression levels of HIF-1αand CYPJ in Cal-27 cells were significantly up-regulated in the hypoxic microenvironment(both P<0.05),which were also significantly enhanced by hyperthermia alone(both P<0.05).Compared with hyperthermia or chemotherapy alone,hyperthermia combined with chemotherapy significantly inhibited the expression of HIF-1αand CYPJ,suppressed cell migration and promoted cell apoptosis(all P<0.05).Conclusions HIF-1αand CYPJ may be potential biomarkers for TSCC tumorigenicity and prognosis.In addition,tumor recurrence after hyperthermia may be due to the role of hyperthermia in triggering HIF-1αexpression,which promotes the growth and survival of tumor cells adaptive to hyperthermia treatment by activating the downstream target genes,while hyperthermia combined with chemotherapy may be a promising tr

关 键 词：舌鳞状细胞癌 Cal-27细胞系 乏氧诱导因子-1Α 亲环素 热疗 

分 类 号：R739.86[医药卫生—肿瘤]