Heteronemin suppresses EGF-induced proliferation through the PI3K/PD-L1 signaling pathways in cholangiocarcinoma

被引：0

作者：

Yang, Yu-Chen S. H. ^{[1
]}

Tsai, Chung-Che ^{[2
,3
]}

Yang, Yung-Ning ^{[4
,5
]}

Liu, Feng-Cheng ^{[6
]}

Lee, Sheng-Yang ^{[7
,8
]}

Yang, Jen-Chang ^{[2
,9
,10
,11
]}

Crawford, Dana R. ^{[12
]}

Chiu, Hsien-Chung ^{[13
,14
]}

Lu, Mei-Chin ^{[15
,16
]}

Li, Zi-Lin ^{[2
,3
]}

Chen, Yi-Chen ^{[2
,3
]}

Chu, Tin-Yi ^{[2
,3
]}

Whang-Peng, Jacqueline ^{[3
,17
]}

Lin, Hung-Yun ^{[3
,18
,19
]}

Wang, Kuan ^{[2
]}

机构：

[1] Taipei Med Univ, Joint Biobank, Off Human Res, Taipei 11031, Taiwan

[2] Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Translat Med, Taipei 11031, Taiwan

[3] Taipei Med Univ, Grad Inst Canc Mol Biol & Drug Discovery, Coll Med Sci & Technol, Taipei 11031, Taiwan

[4] I Shou Univ, Sch Chinese Med Postbaccalaureate, Kaohsiung 84001, Taiwan

[5] I Shou Univ, E Da Hosp, Dept Obstet & Gynecol, Kaohsiung 82445, Taiwan

[6] TriServ Gen Hosp, Div Rheumatol Immunol & Allergy, Taipei, Taiwan

[7] Taipei Med Univ, Coll Oral Med, Sch Dent, Taipei 11031, Taiwan

[8] Taipei Med Univ, Wan Fang Med Ctr, Dent, Taipei 11031, Taiwan

[9] Taipei Med Univ, Coll Biomed Engn, Int PhD Program Biomed Engn, Taipei 11031, Taiwan

[10] Taipei Med Univ, Res Ctr Biomed Device, Taipei 11031, Taiwan

[11] Taipei Med Univ, Res Ctr Digital Oral Sci & Technol, Taipei 11031, Taiwan

[12] Albany Med Coll, Dept Immunol & Microbial Dis, Albany, NY 12208 USA

[13] Natl Def Med Ctr, Sch Dent, Dept Periodontol, 325,Sec 2,Chenggong Rd, Taipei 11490, Taiwan

[14] Triserv Gen Hosp, Taipei 11490, Taiwan

[15] Natl Museum Marine Biol & Aquarium, Pingtung 94450, Taiwan

[16] Natl Dong Hwa Univ, Grad Inst Marine Biol, Pingtung 94450, Taiwan

[17] Taipei Med Univ, Wan Fang Hosp, Canc Ctr, Taipei 11031, Taiwan

[18] Taipei Med Univ, Taipei Med Univ Hosp, Tradit Herbal Med Res Ctr, Taipei 11031, Taiwan

[19] Taipei Med Univ, TMU Res Ctr Canc Translat Med, Taipei 11031, Taiwan

来源：

ONCOLOGY REPORTS | 2025年 / 53卷 / 03期

关键词：

PD-L1; EGF; cancer immunotherapy; cholangiocarcinoma; heteronemin; EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; GEFITINIB RESISTANCE; MAMMALIAN TARGET; GENE-EXPRESSION; BREAST-CANCER; CELLS; KRAS; ACTIVATION; INHIBITORS;

D O I：

10.3892/or.2025.8865

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Epidermal growth factor (EGF) binds with its surface receptor to stimulate gene expression and cancer cell proliferation. EGF stimulates cancer cell growth via phosphoinositide 3-kinase (PI3K) and programmed cell death ligand 1 (PD-L1) pathways. As an integrin alpha v beta 3 antagonist, heteronemin exhibits potent cytotoxic effects against cancer cells. It inhibits critical signal transduction pathways promoted by the EGF. In the current study, EGF-induced signal activation and proliferative effects were investigated in cholangiocarcinoma cells and its molecular targets using qPCR and western blotting analyses. In addition, cell viability assays were performed to assess the growth effects of EGF and heteronemin. Heteronemin reversed the effects of EGF and was further enhanced by blockage of PI3K's activity. In summary, EGF stimulates cholangiocarcinoma cell growth. On the other hand, heteronemin inhibited PI3K activation and PD-L1 expression to reverse the stimulative effects of EGF-induced gene expression and proliferation in cholangiocarcinoma cells.

引用

页数：13

共 51 条

[41] EPIREGULIN - A NOVEL EPIDERMAL GROWTH-FACTOR WITH MITOGENIC ACTIVITY FOR RAT PRIMARY HEPATOCYTES [J].

TOYODA, H ;

KOMURASAKI, T ;

UCHIDA, D ;

TAKAYAMA, Y ;

ISOBE, T ;

OKUYAMA, T ;

HANADA, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (13) :7495-7500

[42] Heteronemin and Tetrac Induce Anti-Proliferation by Blocking EGFR-Mediated Signaling in Colorectal Cancer Cells [J].

Unson, Sukanya ;

Chang, Tung-Cheng ;

Yang, Yung-Ning ;

Wang, Shwu-Huey ;

Huang, Chi-Hung ;

Crawford, Dana R. ;

Huang, Haw-Ming ;

Li, Zi-Lin ;

Lin, Hung-Yun ;

Whang-Peng, Jacqueline ;

Wang, Kuan ;

Davis, Paul J. ;

Li, Wen-Shan .

MARINE DRUGS, 2022, 20 (08)

[43] The power of heteronemin in cancers [J].

Wang, Kuan ;

Chen, Yi-Fong ;

Yang, Yu-Chen S. H. ;

Huang, Haw-Ming ;

Lee, Sheng-Yang ;

Shih, Ya-Jung ;

Li, Zi-Lin ;

Whang-Peng, Jacqueline ;

Lin, Hung-Yun ;

Davis, Paul J. .

JOURNAL OF BIOMEDICAL SCIENCE, 2022, 29 (01)

[44] Common markers of proliferation [J].

Whitfield, ML ;

George, LK ;

Grant, GD ;

Perou, CM .

NATURE REVIEWS CANCER, 2006, 6 (02) :99-106

[45] The epidermal growth factor receptor family: Biology driving targeted therapeutics [J].

Wieduwilt, M. J. ;

Moasser, M. M. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (10) :1566-1584

[46] Aurora-A promotes gefitinib resistance via a NF-κB signaling pathway in p53 knockdown lung cancer cells [J].

Wu, Chun Chi ;

Yu, Chang-Tze Ricky ;

Chang, Gee-Chen ;

Lai, Jin-Mei ;

Hsu, Shih-Lan .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 405 (02) :168-172

[47] Heteronemin, a Spongean Sesterterpene, Induces Cell Apoptosis and Autophagy in Human Renal Carcinoma Cells [J].

Wu, Szu-Ying ;

Sung, Ping-Jyun ;

Chang, Ya-Ling ;

Pan, Shiow-Lin ;

Teng, Che-Ming .

BIOMED RESEARCH INTERNATIONAL, 2015, 2015

[48]

Yabuuchi S, 2009, ANTICANCER RES, V29, P1169

[49] Lovastatin overcomes gefitinib resistance through TNF-α signaling in human cholangiocarcinomas with different LKB1 statuses in vitro and in vivo [J].

Yang, Sheng-Huei ;

Lin, Hung-Yun ;

Chang, Vincent H. S. ;

Chen, Chien-Chung ;

Liu, Yun-Ru ;

Wang, Jinghan ;

Zhang, Keqiang ;

Jiang, Xiaoqing ;

Yen, Yun .

ONCOTARGET, 2015, 6 (27) :23857-23873

[50] Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status [J].

Yang, Yu-Chen S. H. ;

Li, Zi-Lin ;

Huang, Tung-Yung ;

Su, Kuan-Wei ;

Lin, Chi-Yu ;

Huang, Chi-Hung ;

Chen, Han-Yu ;

Lu, Mei-Chin ;

Huang, Haw-Ming ;

Lee, Sheng-Yang ;

Whang-Peng, Jaqueline ;

Lin, Hung-Yun ;

Davis, Paul J. ;

Wang, Kuan .

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2021, 9

← 1 2 3 4 5 6 →