|Table of Contents|

Plumbagin inhibits proliferation and promotes apoptosis of colon cancer cells through CXCL8/PI3K/AKT glycolysis pathway

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

Issue:
2023 03
Page:
411-416
Research Field:
Publishing date:

Info

Title:
Plumbagin inhibits proliferation and promotes apoptosis of colon cancer cells through CXCL8/PI3K/AKT glycolysis pathway
Author(s):
YANG Fang1HOU Qianqian1LI Na1WANG Daqing1CHEN Xiaohua2
1.Hengshui People's Hospital,Hebei Hengshui 053000,China;2.The Fourth Hospital of Hebei Medical University,Hebei Shijiazhuang 050000,China.
Keywords:
plumbagincolon cancerglycolysisCXCL8PI3K/AKT signal pathway
PACS:
R735.3
DOI:
10.3969/j.issn.1672-4992.2023.03.004
Abstract:
Objective:To observe the effect of plumbagin on cell proliferation and apoptosis of Caco-2,and explore its potential mechanism.Methods:Cell count(CCK8) and flow cytometry were used to measure the proliferation inhibition rate and apoptosis rate of Caco-2 cells treated with plumbagin(4,8,12 μmol/L).Caco-2 cells without any treatment were set as the Control group.si-NC group(transfected si-NC) and si-C-X-C motif chemokine ligand 8(CXCL8) group(transfected si-CXCL8) were transfected into Caco-2 cells by liposome method.Caco-2 cells treated with 8 μmol/L plumbagin and 0.5% DMSO were set as 8 μmol/L+DMSO group.Caco-2 cells treated with 8 μmol/L plumbagin and z-VAD-FMK or 740Y-P were set as 8 μmol/L+z-VAD-FMK group,8 μmol/L+740Y-P group,respectivly.The mRNA and protein expression of CXCL8 were measred by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB).CXCL8,M2 pyruvate kinase(PKM2),glyceraldehyde-3-phosphate dehydrogenase(LDHA),human α-enolase(ENO1),glucose phosphate isomerase(GPI),phosphorylated phosphatidylinositol 3 kinase(p-PI3K) and phosphorylated protein kinase B(p-Akt) were measred by Western blot.Results:Compared with the Control group,plumbagin(4,8,12 μmol/L) promoted the proliferation inhibition rate and apoptosis rate of Caco-2 cells and inhibited the mRNA and protein expression of CXCL8 in a concentration dependent manner.Compared with 8 μmol/L+DMSO group,the proliferation inhibition rate and apoptosis rate significantly decreased,and the mRNA and protein expression of CXCL8 significantly increased in 8 μmol/L+z-VAD-FMK group(P<0.05).Plumbagin(4,8,12 μmol/L) inhibited the protein expression of PKM2,LDHA,p-PI3K and p-AKT in a concentration dependent manner.The protein expressions of PKM2,LDHA,p-PI3K and p-AKT in si-CXCL8 group were significantly lower than those in si-NC group.740Y-P significantly weakened the promoting effect of plumbagin on the proliferation inhibition rate and apoptosis rate of Caco-2 cells.Conclusion:Plumbagin could inhibit the proliferation and promote apoptosis of colon cancer cells,and its potential mechanism may be related to CXCL8/PI3K/AKT glycolysis pathway.

References:

[1]CAO W,CHEN HD,YU YW,et al.Changing profiles of cancer burden worldwide and in China:a secondary analysis of the global cancer statistics 2020[J].Chin Med J(Engl),2021,134(7):783-791.
[2]MITSUMA A,ANDO Y.Chemotherapy for older patients with cancer[J].Gan To Kagaku Ryoho,2022,49(1):13-18.
[3]ALILU L,HEYDARZADEH L,HABIBZADEH H,et al.The effect of peer education on management of chemotherapy side effects in patients with cancer[J].Iran J Nurs Midwifery Res,2021,26(1):81-84.
[4]SURYA KANT TRIPATHI,MUNMUN PANDA,BIJESH K BISWAL,et al.Emerging role of plumbagin:Cytotoxic potential and pharmaceutical relevance towards cancer therapy[J].Food Chem Toxicol,2019,125(3):566-582.
[5]LIU Q,LI A,TIAN Y,et al.The CXCL8-CXCR1/2 pathways in cancer[J].Cytokine Growth Factor Rev,2016,31(10):61-71.
[6]ALZAHRANI AS.PI3K/Akt/mTOR inhibitors in cancer:At the bench and bedside[J].Semin Cancer Biol,2019,59(12):125-132.
[7]NAVDEEP S CHANDEL.Glycolysis[J].Cold Spring Harb Perspect Biol,2021,13(5):a040535.
[8]刘欢,梁丽英,刘显,等.白花丹醌对人结肠腺癌Caco-2细胞凋亡、自噬及PI3K/Akt/mTOR信号通路的影响[J].中国病理生理杂志,2021,37(2):255-262. LIU H,LIANG LY,LIU X,et al.Effects of Plumbago quinone on apoptosis,autophagy and PI3K/Akt/mTOR signaling pathway of human colon adenocarcinoma Caco-2 cells[J].Chinese Journal of Pathophysiology,2021,37(2):255-262.
[9]李奕璇.中药单体白花丹醌通过调控VEGF/VEGFR2信号通路抑制结肠癌血管生成的实验研究[J].实用药物与临床,2018,21(7):745-749. LI YX.Experimental study on inhibiting angiogenesis of colon cancer by regulating VEGF/VEGFR2 signal pathway[J].Practical Drugs and Clinic,2018,21(7):745-749.
[10]FISHER RC,BELLAMKONDA K,ALEX MOLINA L,et al.Disrupting inflammation-associated CXCL8-CXCR1 signaling inhibits tumorigenicity initiated by sporadic-and colitis-colon cancer stem cells[J].Neoplasia,2019,21(3):269-281.
[11]RASOOL M,NATESAN PUSHPARAJ P,KARIM S.Overexpression of CXCL8 gene in Saudi colon cancer patients[J].Saudi J Biol Sci,2021,28(11):6045-6049.
[12]BISHNUPURI KS,ALVARADO DM,KHOURI AN,et al.IDO1 and kynurenine pathway metabolites activate PI3K-Akt signaling in the neoplastic colon epithelium to promote cancer cell proliferation and inhibit apoptosis[J].Cancer Res,2019,79(6):1138-1150.
[13]SHEN T,YANG ZB,CHENG XS,et al.CXCL8 induces epithelial-mesenchymal transition in colon cancer cells via the PI3K/Akt/NF-κB signaling pathway[J].Oncol Rep,2017,37(4):2095-2100.
[14]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.
[15]ABBASZADEH Z,CESMELI S,BIRAY AVCI S.Crucial players in glycolysis:Cancer progress[J].Gene,2020,726(2):144158.
[16]FENG Y,XIONG Y,QIAO T,et al.Lactate dehydrogenase A:A key player in carcinogenesis and potential target in cancer therapy[J].Cancer Med,2018,7(12):6124-6136.
[17]GANAPATHY-KANNIAPPAN S,GESCHWIND JF.Tumor glycolysis as a target for cancer therapy:progress and prospects[J].Mol Cancer,2013,12(11):152.

Memo

Memo:
河北省衡水市科技计划(编号:2019014032Z)
Last Update: 2022-12-30