GANT61 Induces Colon Cancer Cell Apoptosis by Regulating Autophagy
10.3969/j.issn.1008-7125.2024.12.006
- VernacularTitle:GANT61通过调控自噬诱导结肠癌细胞凋亡
- Author:
Hong ZHANG
1
;
Jianguo ZHANG
;
Miao HE
;
Zheng YUAN
;
Han FANG
;
Changfa YU
;
Qingqing XIA
Author Information
1. 温州医科大学附属黄岩医院 台州市第一人民医院检验科(318000)
- Publication Type:Journal Article
- Keywords:
GANT61;
Colon Neoplasms;
Autophagy;
Apoptosis
- From:
Chinese Journal of Gastroenterology
2024;29(12):731-736
- CountryChina
- Language:Chinese
-
Abstract:
Background:Colorectal cancer is a common malignant tumor of the digestive system,its incidence rate is increasing and seriously affect human health.Aims:To investigate whether GANT61,an inhibitor of Hedgehog signaling pathway,induces apoptosis of colon cancer cells by regulating autophagy.Methods:Colon cancer cell line SW480 was cultured in vitro and treated with GANT61 of different concentrations(0,10,20,and 40 μmol/L)for 24 h.The cell viability was measured by CCK-8 assay,and the apoptosis rate was determined by flow cytometry.Expressions of the key molecules in Hedgehog/GLI signaling pathway,as well as the proteins related to autophagy and apoptosis were detected by Western blotting and/or qRT-PCR.Then the SW480 cells were treated with combination of GANT61 and chloroquine,an autophagy inhibitor,or rapamycin,an autophagy agonist,the alterations of the apoptosis rates and the related protein expressions were assessed.Results:The viability of SW480 cells decreased and the apoptosis rate increase with the increase of GANT61 concentration.Meanwhile,the mRNA and protein expressions of GLI1,GLI2,cyclin D1(a cell cycle G1/S-specific protein),and BCL-2(an anti-apoptotic protein)were inhibited,and the protein expressions of C-PARP1(an apoptosis-related protein)and BECLIN1,LC3Ⅱ(autophagy-related proteins)were increased.Chloroquine could partially reverse the effect of GANT61 on autophagy activation and cell apoptosis,while rapamycin could promote the pro-apoptotic effect of GANT61.Conclusions:GANT61 can activate autophagy and induce apoptosis in colon cancer cells.
