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Archive > Volume 29 Issue 11 > 2022,29(11):1025-1031. DOI:10.3872/j.issn.1007-385X.2022.11.013 Prev Next
Basic Research
Mechanism of transcription factor SP1 affecting drug resistance of small cell lung cancer H446/DDP cells by regulating ABCC1
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Abstract:
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.
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