大黄素抑制胃癌AGS细胞YAP1、FOXD1基因表达及相关机制

doi:10.3969/j.issn.1006-5725.2024.01.011

Abstract

Abstract:

Objective To explore the possible mechanism of emodin in inhibiting proliferation， migration， and invasion of AGS cells and in suppressing the expressions of YAP1 and FOXD1. Methods Normal gastric cell GES-1 and gastric cancer cell AGS were cultured with different concentrations of emodin. CCK8 test， scratch test and Transwell assay were used to verify changes in the biological phenotype of AGS cells. TCGA database was applied to analyze expressions of HK2， YAP1 and FOXD1 in gastric cancer tissues and normal gastric tissues. Western blotting method was used to detect the impacts of emodin on HK2，YAP1 and FOXD1 proteins in AGS cells. Exogenous pyruvic acid was added to verify the changes in YAP1 and FOXD1. Results The IC50 of emodin was significantly higher in GES-1 cells than in AGS cells （P < 0.05）. CCK8 proliferation test， scratch test， and Transwell assay showed that emodin significantly inhibited the biological abilities of AGS （P < 0.05 for comparisons）. Analysis on the TCGA bioinformatics database found that the expression of key enzymes HK2 in the glycolysis pathway and oncogenes YAP1 and FOXD1 was significantly higher in gastric cancer tissues than in normal gastric tissues （P < 0.05 for comparisons）. Emodin significantly inhibited the protein expressions of key glycolytic enzymes HK2 and oncogenes YAP1 and FOXD1 （P < 0.05 for comparisons）. With supplement of exogenous glycolytic metabolite pyruvate， the protein expressions of oncogenes YAP1 and FOXD1 significantly increased （P < 0.05 for comparisons）. Conclusions Emodin has a significant pharmacological inhibitory effect on gastric cancer AGS cells， markedly suppressing their biological phenotype. Emodin not only significantly inhibits the key enzyme HK2 in glycolysis metabolism， but also the protein expressions of oncogenes YAP1 and FOXD1. With the addition of exogenous pyruvate to enhance the glycolytic metabolic pathway， the protein expressions of oncogenes YAP1 and FOXD1 significantly increased. The above results suggest a close association of YAP1 and FOXD1 with glycolytic metabolism. Emodin may inhibit oncogenes YAP1 and FOXD1 through the glycolytic metabolism of gastric cancer AGS cells.

Key words: emodin, gastric cancer, HK2, YAP1, FOXD1, glycolytic metabolism

CLC Number:

R285.5

Tian GU,Chunhong LIU,Fei ZHANG,Wei QIAN,Yanqiu ZHU,Mingliang CHU,Jiemin. LIU. The mechanism of emodin inhibiting YAP1 and FOXD1 in gastric cancer AGS cells and its related study[J]. The Journal of Practical Medicine, 2024, 40(1): 59-64.

Figures/Tables 6

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References 24

1	SIEGEL R L， MILLER K D， JEMAL A. Cancer statistics， 2020［J］. CA Cancer J Clin， 2020，70（1）：7-30.
2	郑荣寿，张思维，孙可欣，等. 2016年中国恶性肿瘤流行情况分析［J］. 中华肿瘤杂志， 2023，45（3）：212-220.
3	林潼，张湘苑，沈梦菲，等. 重构本草——大黄［J］. 吉林中医药， 2023，43（2）：215-217.
4	何欣，刘云鹏，李冬阳，等. 基于网络药理学和分子对接预测大黄治疗胃癌的作用机制［J］. 中国医科大学学报， 2023，52（1）：6-11， 17.
5	VAUPEL P， SCHMIDBERGER H， MAYER A. The Warburg effect： essential part of metabolic reprogramming and central contributor to cancer progression［J］. Int J Radiat Biol， 2019，95（7）：912-919.
6	XIE K， FENG J， FAN D， et al. BARX2/FOXA1/HK2 axis promotes lung adenocarcinoma progression and energy metabolism reprogramming［J］. Transl Lung Cancer Res， 2022，11（7）：1405-1419.
7	耿西林，龙卫红，海军，等. 己糖激酶2在肝癌转移中的调控作用［J］. 中华肿瘤杂志， 2016，38（10）：739-742.
8	李兰兰，付生军，陶燕，等. HK2基因表达与泌尿系肿瘤的发生、免疫细胞浸润及预后的相关性分析［J］. 暨南大学学报（自然科学与医学版）， 2021，42（1）：40-47.
9	DONMEZ C， KONAC E. Silencing effects of FOXD1 inhibit metastatic potentials of the PCa via N-cadherin - Wnt/β-catenin crosstalk［J］. Gene， 2022，836：146680.
10	CAI K， CHEN S， ZHU C， et al. FOXD1 facilitates pancreatic cancer cell proliferation， invasion， and metastasis by regulating GLUT1-mediated aerobic glycolysis［J］. Cell Death Dis， 2022，13（9）：765.
11	NAKAYAMA S， SOEJIMA K， YASUDA H， et al. FOXD1 expression is associated with poor prognosis in non-small cell lung cancer［J］. Anticancer Res， 2015，35（1）：261-268.
12	CHANDRASHEKAR D S， KARTHIKEYAN S K， KORLA P K， et al. UALCAN： An update to the integrated cancer data analysis platform［J］. Neoplasia， 2022，25：18-27.
13	HERENG T H， ELGSTØEN K B， CEDERKVIST F H， et al. Exogenous pyruvate accelerates glycolysis and promotes capacitation in human spermatozoa［J］. Hum Reprod， 2011，26（12）：3249-3263.
14	LORDICK F， CARNEIRO F， CASCINU S， et al. Gastric cancer： ESMO Clinical Practice Guideline for diagnosis， treatment and follow-up［J］. Ann Oncol， 2022，33（10）：1005-1020.
15	NORWOOD D A， MONTALVAN E E， DOMINGUEZ R L， et al. Gastric Cancer： Emerging Trends in Prevention， Diagnosis， and Treatment［J］. Gastroenterol Clin North Am， 2022，51（3）：501-518.
16	HARVEY K， TAPON N. The Salvador-Warts-Hippo pathway-an emerging tumour-suppressor network［J］. Nat Rev Cancer， 2007，7（3）：182-191.
17	黄翠霞，张雅倩，杨爱萍，等. 基于Hippo/YAP信号通路探讨穿心莲内酯抗三阴性乳腺癌的作用机制［J］. 实用医学杂志， 2023， 39（16）： 2050-2056.
18	YAO W， GUO P， MU Q， et al. Exosome-Derived Circ-PVT1 Contributes to Cisplatin Resistance by Regulating Autophagy， Invasion， and Apoptosis Via miR-30a-5p/YAP1 Axis in Gastric Cancer Cells［J］. Cancer Biother Radiopharm， 2021，36（4）：347-359.
19	陈达. YAP1通过调控肿瘤相关巨噬细胞的糖代谢促进胃癌对5-Fu的化疗抵抗［D］. 南方医科大学临床医学（八年制）， 2020.
20	BOND K H， FETTING J L， LARY C W， et al. FOXD1 regulates cell division in clear cell renal cell carcinoma［J］. BMC Cancer， 2021，21（1）：312.
21	CHEN C， XU Z Q， ZONG Y P， et al. CXCL5 induces tumor angiogenesis via enhancing the expression of FOXD1 mediated by the AKT/NF-κB pathway in colorectal cancer［J］. Cell Death Dis， 2019，10（3）：178.
22	HUANG J， LIANG B， WANG T. FOXD1 expression in head and neck squamous carcinoma： a study based on TCGA， GEO and meta-analysis［J］. Biosci Rep， 2021，41（7）.
23	ZHAO Y F， ZHAO J Y， YUE H， et al. FOXD1 promotes breast cancer proliferation and chemotherapeutic drug resistance by targeting p27［J］. Biochem Biophys Res Commun， 2015，456（1）：232-237.
24	WANG Z， CHENG Y， ZHU Y， et al. Long non-coding RNA FOXD1-AS1 promotes the progression and glycolysis of nasopharyngeal carcinoma by sustaining FOXD1 expression［J］. Am J Cancer Res， 2020，10（11）：3686-3704.

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The mechanism of emodin inhibiting YAP1 and FOXD1 in gastric cancer AGS cells and its related study

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