目的：探讨敲减转录因子特异蛋白1（SP1）对小细胞肺癌（SCLC）H466/DDP 细胞顺铂（DDP）耐药的影响及其分子机 制。方法：构建敲减SP1同时过表达ATP 结合盒亚家族C 成员1（ABCC1）的SCLC H466/DDP 细胞，采用IHC 法检测SP1、 ABCC1 在非耐药和耐药SCLC 组织中的表达，用Spearman r 法分析SP1 与ABCC1 在SCLC 组织中表达的相关性；WB 法检测 SP1、ABCC1、CD44 在转染后H446/DDP 细胞中的表达；CCK-8 法、FCM 术、微球实验检测转染后H446/DDP 细胞的增殖、凋亡及 自我复制能力的变化；染色质免疫共沉淀（CHIP）实验检测SP1 是否是ABCC1 的转录因子。结果：耐药细胞H446/DDP 和耐药 SCLC 组织中的SP1、ABCC1 蛋白水平均高于H446 细胞和非耐药SCLC 组织（均P<0.05），SCLC 组织中的SP1、ABCC1 蛋白表达 呈正相关；敲减SP1 抑制H446/DDP 细胞的增殖活力，降低CD44、ABCC1 蛋白表达水平、减少细胞微球形成数（均P<0.05），促进 细胞凋亡（P<0.05）；SP1 是ABCC1 的转录因子。结论：转录因子SP1 通过调控ABBC1 的表达影响SCLC H446/DDP 细胞的耐 药，SP1 是SCLC 对DDP 耐药的潜在治疗靶点。

Objective: To investigate the effect of transcription factor specificity protein 1 (SP1) knockdown on cisplatin (DDP) resistance in small cell lung cancer (SCLC) H466/DDP cells and its molecular mechanism. Methods: SCLC H466/DDP cells with knockdown of SP1 and simultaneous overexpression of ATP binding cassette subfamily C member 1（ABCC1）were constructed, and the expression of SP1 and ABCC1 in non-drug-resistant and drug-resistant SCLC tissues was detected by IHC method. The correlation between SP1 and ABCC1 expression in SCLC tissues was analyzed by the Spearman r method. Western blot was performed to detect the expression of SP1, ABCC1 and CD44 in transfected H446/DDP cells. The proliferation, apoptosis and self-replication ability of H446/DDP cells were detected by CCK-8, flow cytometry and microsphere assay respectively. Chromatin immunoprecipitation (ChIP) assay was performed to detect whether SP1 is a transcription factor of ABCC1. Results: The protein levels of SP1 and ABCC1 in drug-resistant H446/DDP cells and drug-resistant SCLC tissues were higher than those in parental H446 cells and non-drug-resistant SCLC tissues (all P<0.05), and the expression of SP1 and ABCC1 protein in SCLC tissues was positively correlated. Knockdown of SP1 inhibited the proliferation ability, reduced CD44 and ABCC1 protein expression levels, decreased the number of cell microsphere formation, and promoted apoptosis (all P<0.05) of H446/DDP cells. SP1 was approved to be the transcription factor of ABCC1. Conclusion: Transcription factor SP1 is involved in drug resistance in SCLC H446/DDP cells by regulating ABBC1 expression, and SP1 is a potential therapeutic target for DDP-resistant SCLC.

黑龙江省省属高等学校基本科研业务费资助项目（No.2019-KYYWF-0983）