肿瘤预防与治疗2023,Vol.36Issue(12):1009-1015,7.DOI:10.3969/j.issn.1674-0904.2023.12.005
HDAC3影响二甲双胍抑制非小细胞肺癌增殖的实验研究
Experimental Study on the Effect of HDAC3 on Metformin Inhibiting the Proliferation of Non-Small Cell Lung Cancer
摘要
Abstract
Objective:To investigate the effect of metformin on the proliferation of non-small cell lung cancer cells and elucidate the role of HDAC3 in it.Methods:Human non-small cell lung cancer cell lines(H460 cells,H1299 cells and A549 cells)were treated with different concentrations of metformin in vitro,and the effects of metformin on cell proliferation were detected by CCK-8 and Ki-67 staining.Lung cancer(H1299 cells and A549 cells)transplantation tumor models were established to determine the an-ti-tumor efficacy of metformin in vivo.HDAC3 over-expression in H1299 cells was mediated by lentivirus,and proteomics analysis was used to explore the effect and mechanism of HDAC3 over-ex-pression on metformin inhibiting the proliferation of lung cancer cells.Results:In vitro experiments showed that metformin in-hibited the cell viability and proliferation of multiple non-small cell lung cancer cell lines in a dose-dependent manner.In vivo experiments demonstrated that metformin significantly reduced the tumor volume and weight as well as had no significant effect on body weight of mice.Furthermore,metformin inhibited the expression of HDAC3 in lung cancer cells,while HDAC3 over-expression significantly reduced the effect of metformin inhibiting the proliferation of lung cancer cells.Proteomics analysis revealed that differential proteins screened by metformin-treated H1299 cells with over-expression of HDAC3 are mainly enriched in HIF-1 pathway and glucose metabolism-related pathway.Conclusion:Metformin has anti-tumor effect in vitro and in vivo,and over-expression of HDAC3 can inhibit this effect.Targeting HDAC3 may become a new strategy for the treatment of non-small cell lung cancer with metformin.关键词
非小细胞肺癌/二甲双胍/HDAC3/增殖Key words
Non-small cell lung cancer/Metformin/HDAC3/Proliferation分类
生物科学引用本文复制引用
唐小淋,卢从华,毕万达,王治国,林采余,何勇,李力..HDAC3影响二甲双胍抑制非小细胞肺癌增殖的实验研究[J].肿瘤预防与治疗,2023,36(12):1009-1015,7.基金项目
This study was supported by grants from Chongqing Science and Technology Bureau(No.CSTB2023N-SCQ-JQX0033,No.CSTB2022NSCQ-MSX1110). 重庆市杰出青年科学基金(编号:CSTB 2023NSCQ-JQX0033) (No.CSTB2023N-SCQ-JQX0033,No.CSTB2022NSCQ-MSX1110)
重庆市自然科学基金面上项目(编号:CSTB2022NSCQ-MSX1110) (编号:CSTB2022NSCQ-MSX1110)