|Table of Contents|

Sodium butyrate inhibits the growth of colorectal cancer cells by promoting autophagic degradation of HIF-1α

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2022 05
Page:
762-767
Research Field:
Publishing date:

Info

Title:
Sodium butyrate inhibits the growth of colorectal cancer cells by promoting autophagic degradation of HIF-1α
Author(s):
ZHANG Qiuyu; BIAN Zhongbo; SUN Xiaodie; QIN Yong; LIU Huahuan; MAO Lianzhi; SUN Suxia
Department of Nutrition and Food Hygiene,School of Public Health,Southern Medical University,Guangdong Guangzhou 510515,China.
Keywords:
colorectal cancer; NaB; autophagy; HIF-1α
PACS:
R735.3+4
DOI:
10.3969/j.issn.1672-4992.2022.05.002
Abstract:
Objective:The purpose of this study was to explore the effect of sodium butyrate(NaB) on the growth of colorectal cancer cells and its possible mechanisms.Methods:HCT116 cells were treated with NaB（0,1,2,5,10 mmol/L） for 24 h.Cell viability and clonogenic ability were assessed with MTT assay and plate cloning experiment,respectively.Real-time PCR and Western blot were used to detect the expression of hypoxia inducible factor-1α(HIF-1α) and lactate dehydrogenase-A(LDHA).HCT116 cells were treated with 3-methyl adenine(3-MA),chloroquine(CQ),protein synthesis inhibitor(CHX),proteasome inhibitor(MG132) or cobalt chloride(CoCl2) and then expoured to 5 mmol/L NaB.The expression of LC3Ⅱ and HIF-1α were detected by Western blot.Cell viability were assessed with MTT assay.Results:In comparison with the control cells,2 mmol/L NaB significantly inhibited the viability and clonogenic ability of HCT116 cells(P<0.01),and down-regulated the expressions of HIF-1α and LDHA(P<0.01).The production of LC3Ⅱ was blocked by 5 mmol/L 3-MA(P<0.05),which inhibited the effect of NaB on LC3Ⅱ(P<0.05).Treatment with 50 μmol/L CQ can promote the accumulation of LC3Ⅱ(P<0.01) and up-regulate the level of LC3Ⅱ protein induced by NaB(P<0.05).Treatment with 200 μmol/L CHX for 5 h repressed HIF-1α(P<0.05),and NaB advanced the time of decreasing HIF-1α protein level to 1 h(P<0.01).Treatment of HCT116 cells with CQ alleviated the inhibitory effects of NaB on HIF-1α,LDHA and cell viability(P<0.05),while MG132 and CoCl2 did not affect the inhibitory effects of NaB on HCT116 cells(P>0.05).Conclusion:NaB down-regulates the stability of HIF-1α protein through autophagy,and then inhibits the expression of its downstream protein LDHA,so as to inhibit the growth of colorectal cancer cells.

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Memo

Memo:
National Natural Science Foundation of China(No.81773429）；国家自然科学基金（编号：81773429）
Last Update: 2022-01-27