摘要
目的探讨NQO1蛋白在皮肤鳞状细胞癌(cutaneous squamous cell carcinoma,CSCC)组织中的表达及β-Lapachone在CSCC中的抗肿瘤作用。方法采用免疫组化法检测76例CSCC组织和13例正常皮肤组织中NQO1的表达;分析NQO1表达与CSCC临床病理特征的关系;体外常规培养A431细胞,通过克隆形成、流式细胞术及免疫荧光染色法检测β-Lapachone对细胞增殖、周期进程以及活性氧(reactive oxygen species,ROS)生成的作用,并通过Western blot检测相关分子和信号通路。结果免疫组化:NQO1蛋白在CSCC中的阳性率(85.5%,65/76)高于正常皮肤组织(46.2%,6/13,P<0.05)。χ^(2)检验:NQO1蛋白表达与肿瘤大小有关(P<0.05),与患者年龄、性别、分化和临床分期均无相关性。MTT和克隆形成实验:β-Lapachone可抑制A431细胞的增殖能力。流式细胞术检测:β-Lapachone诱导A431细胞发生周期阻滞。β-Lapachone可促进细胞生成ROS,激活JNK信号通路。结论NQO1在CSCC中高表达,其生物激活剂β-Lapachone可通过调控多种生物学功能,进而抑制CSCC的恶性演进。
Purpose To evaluate the expression level of NQO1 in cutaneous squamous cell carcinoma(CSCC),and to investigate the anti-neoplastic potential ofβ-Lapachone in CSCC.Methods Immunohistochemical(IHC)staining was performed to evaluate the expression level of NQO1 in 76 CSCC tissues and 13 normal skin tissues.The relationship between NQO1 expression and pathological parameters of CSCC patients was analyzed by Chi-square test.In addition,the functions ofβ-Lapachone on cancer proliferation,cell cycle progression and reactive oxygen species(ROS)generation were detected by colony formation,flow cytometry and immunofluorescence(IF)staining.Then,the related regulators and signaling pathways were detected by Western blot.Results IHC showed that the positive rate of NQO1 in CSCC(85.5%,65/76)was significantly higher than that in normal tissues(46.2%,6/13,P<0.05).Chi-square test showed that high expression of NQO1 was related to tumor size(P<0.05),but not age,gender,differentiation,and clinical stage.MTT and colony formation assay showed thatβ-Lapachone inhibited the A431 cell proliferation of CSCC.In addition,flow cytometry analysis showed thatβ-Lapachone induced cell cycle arrest.Moreover,IF staining and Western blot showed thatβ-Lapachone facilitated the generation of ROS and JNK pathway activation.Conclusion NQO1 is highly expressed in CSCC,and its bioactivatable drug,β-Lapachone inhibits the malignant progression of CSCC by regulating various biological functions.
作者
赵磊
王姝昊
孙紫洋
崔英
李柱虎
朴俊杰
朱莲花
ZHAO Lei;WANG Shu-hao;SUN Zi-yang;CUI Ying;LI Zhu-hu;PIAO Jun-jie;ZHU Lian-hua(Medical College,Yanbian University,Yanji 133002,China;Department of Dermatology,Affiliated Hospital of Yanbian University,Yanji 133002,China)
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2022年第2期187-190,196,共5页
Chinese Journal of Clinical and Experimental Pathology
基金
国家自然科学基金(81860549)。
