Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2

Objective To explore the effects of Timosaponin (TMS) on lung cancer and cancer stem cell (CSC) and its underlying mechanism. Methods MTS, Hoechst 33342 staining, flow cytometry, cell migration and plate cloning experiments were used to detect the effect of TMS on cell biological functions. The effe...

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Main Authors: CAO Song, YAN Xiaoyan, MA Jun, JING Wenjiang, ZHANG Shulian, WANG Juanyi, LI Xiang, WU Xiang
Format: Article
Language:zho
Published: Magazine House of Cancer Research on Prevention and Treatment 2020-08-01
Series:Zhongliu Fangzhi Yanjiu
Subjects:
Online Access:http://html.rhhz.net/ZLFZYJ/html/8578.2020.20.0109.htm
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author CAO Song
YAN Xiaoyan
MA Jun
JING Wenjiang
ZHANG Shulian
WANG Juanyi
LI Xiang
WU Xiang
author_facet CAO Song
YAN Xiaoyan
MA Jun
JING Wenjiang
ZHANG Shulian
WANG Juanyi
LI Xiang
WU Xiang
author_sort CAO Song
collection DOAJ
description Objective To explore the effects of Timosaponin (TMS) on lung cancer and cancer stem cell (CSC) and its underlying mechanism. Methods MTS, Hoechst 33342 staining, flow cytometry, cell migration and plate cloning experiments were used to detect the effect of TMS on cell biological functions. The effect of TMS on tumor ball formation was measured and confirmed by the ADELFLUOR. RT-qPCR and Western blot were applied to detect the effect of TMS on key genes and proteins in Hedgehog signaling pathway and CSC, and the effect of SMO and SOX2 protein on tumor sphere formation were evaluated by siRNA transfection. Results TMS can inhibit the proliferation of lung cancer cells and the growth of CSCs. TMS can reduce the protein expression levels of GLI1, GLI2 and SMO, and siRNA targeting SMO can inhibit the formation of tumor spheres. In addition, TMS can reduce the transcription and protein expression of SOX2, while siRNA targeting SOX2 can inhibit the formation of tumorspheres. TMS inhibited the formation of lung CSC by regulating the expression of GLI1, GLI2, SMO, and SOX2. Conclusion TMS could regulate Hedgehog signaling pathway-mediated SOX2 to suppress the formation of lung cancer stem cells, thereby inhibiting the proliferation and migration of lung cancer cells, which lays the foundation for targeting Hedgehog signaling pathway and SOX2 in the treatment of lung cancer.
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spelling doaj.art-78a82dc912a04a2897319ec7ce6b6ba22022-12-22T01:23:06ZzhoMagazine House of Cancer Research on Prevention and TreatmentZhongliu Fangzhi Yanjiu1000-85781000-85782020-08-0147859059510.3971/j.issn.1000-8578.2020.20.01098578.2020.20.0109Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2CAO Song0YAN Xiaoyan1MA Jun2JING Wenjiang3ZHANG Shulian4WANG Juanyi5LI Xiang6WU Xiang7Department of Oncology, 3201 Hospital Affiliated to The School of Medicine of Xi'an Jiaotong University, Hanzhong 723000, ChinaDepartment of Oncology, 3201 Hospital Affiliated to The School of Medicine of Xi'an Jiaotong University, Hanzhong 723000, ChinaDepartment of Oncology, 3201 Hospital Affiliated to The School of Medicine of Xi'an Jiaotong University, Hanzhong 723000, ChinaDepartment of Oncology, 3201 Hospital Affiliated to The School of Medicine of Xi'an Jiaotong University, Hanzhong 723000, ChinaDepartment of Oncology, 3201 Hospital Affiliated to The School of Medicine of Xi'an Jiaotong University, Hanzhong 723000, ChinaDepartment of Oncology, 3201 Hospital Affiliated to The School of Medicine of Xi'an Jiaotong University, Hanzhong 723000, ChinaDepartment of Oncology, 3201 Hospital Affiliated to The School of Medicine of Xi'an Jiaotong University, Hanzhong 723000, ChinaSchool of Basic Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an 710012, ChinaObjective To explore the effects of Timosaponin (TMS) on lung cancer and cancer stem cell (CSC) and its underlying mechanism. Methods MTS, Hoechst 33342 staining, flow cytometry, cell migration and plate cloning experiments were used to detect the effect of TMS on cell biological functions. The effect of TMS on tumor ball formation was measured and confirmed by the ADELFLUOR. RT-qPCR and Western blot were applied to detect the effect of TMS on key genes and proteins in Hedgehog signaling pathway and CSC, and the effect of SMO and SOX2 protein on tumor sphere formation were evaluated by siRNA transfection. Results TMS can inhibit the proliferation of lung cancer cells and the growth of CSCs. TMS can reduce the protein expression levels of GLI1, GLI2 and SMO, and siRNA targeting SMO can inhibit the formation of tumor spheres. In addition, TMS can reduce the transcription and protein expression of SOX2, while siRNA targeting SOX2 can inhibit the formation of tumorspheres. TMS inhibited the formation of lung CSC by regulating the expression of GLI1, GLI2, SMO, and SOX2. Conclusion TMS could regulate Hedgehog signaling pathway-mediated SOX2 to suppress the formation of lung cancer stem cells, thereby inhibiting the proliferation and migration of lung cancer cells, which lays the foundation for targeting Hedgehog signaling pathway and SOX2 in the treatment of lung cancer.http://html.rhhz.net/ZLFZYJ/html/8578.2020.20.0109.htmlung cancerstem cellstimosaponinhedgehog signaling pathwaysox2
spellingShingle CAO Song
YAN Xiaoyan
MA Jun
JING Wenjiang
ZHANG Shulian
WANG Juanyi
LI Xiang
WU Xiang
Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2
Zhongliu Fangzhi Yanjiu
lung cancer
stem cells
timosaponin
hedgehog signaling pathway
sox2
title Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2
title_full Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2
title_fullStr Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2
title_full_unstemmed Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2
title_short Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2
title_sort timosaponin inhibit proliferation and stem cell formation of lung cancer through regulating hedgehog signaling mediated sox2
topic lung cancer
stem cells
timosaponin
hedgehog signaling pathway
sox2
url http://html.rhhz.net/ZLFZYJ/html/8578.2020.20.0109.htm
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