Paeoniflorin inhibits programmed cell death-1-ligand 1 expression in HepG2 cells by regulating JAK/STAT3 signal pathway

WAN Nanyan; JIANG Cuihua; GAO Meng; ZHANG Jian; YIN Zhiqi; PAN Ke

doi:10.11665/j.issn.1000-5048.20190213

Journal of China Pharmaceutical University > 2019 > 50(2): 213-221. > DOI: 10.11665/j.issn.1000-5048.20190213

WAN Nanyan, JIANG Cuihua, GAO Meng, ZHANG Jian, YIN Zhiqi, PAN Ke. Paeoniflorin inhibits programmed cell death-1-ligand 1 expression in HepG2 cells by regulating JAK/STAT3 signal pathway[J]. Journal of China Pharmaceutical University, 2019, 50(2): 213-221. DOI: 10.11665/j.issn.1000-5048.20190213

Citation:

PDF (2890 KB)

Paeoniflorin inhibits programmed cell death-1-ligand 1 expression in HepG2 cells by regulating JAK/STAT3 signal pathway

WAN Nanyan^1,2,3,4,
JIANG Cuihua^2,3,
GAO Meng^2,3,
ZHANG Jian^2,3,
YIN Zhiqi⁴,
PAN Ke¹

More Information

Graphical Abstract

Abstract

Abstract

In order to explore the effect and its mechanism of paeoniflorin on PD-L1, a PD-L1 high expression cell model was established in interferon gamma(IFN-γ)-induced HepG2 cells. The cytotoxicity of paeoniflorin was detected by MTT assay. Flow cytometry, ELISA and RT-PCR were performed to detect protein and mRNA levels of PD-L1 regulated by paeoniflorin. In HepG2 cells and Jurkat T cell co-culture system, the expression of IL-2 was detected by ELISA. Besides, T cell proliferation was evaluated by CCK-8 method, and the protein expression levels of PD-L1, JAK and STAT3 after drug treatment were determined by Western blot. These results indicated that paeoniflorin could significantly down-regulate the levels of PD-L1 protein and mRNA. In addition, it increased the number of T cells and the concentration of IL-2 in the co-culture system. Furthermore, paeoniflorin could significantly inhibit the protein expression of JAK and STAT3. Au the above experimental data indicated that paeoniflorin could down-regulate the expression of PD-L1, and its mechanism might be related to the JAK/STAT3 pathway.
- paeoniflorin,
- PD-L1,
- tumor immune escape,
- immune checkpoint

FullText(HTML)

References (30)

References

[1]	Jemal A,Bray F,Center MM,et al.Global cancer statistics[J].Ca Cancer J Clin,2011,61(2):69-90.
[2]	Gao Q,Wang XY,Qiu SJ,et al.Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma[J].Clin Cancer Res,2009,15(3):971-979.
[3]	Zhou J,Liu M,Sun H,et al.Hepatoma-intrinsic CCRK inhibition diminishes myeloid-derived suppressor cell immunosuppression and enhances immune-checkpoint blockade efficacy[J].Gut,2017,67(5):gutjnl-2017-314032.
[4]	Dai X,Pi G,Yang SL,et al.Association of PD-L1 and HIF-1α coexpression with poor prognosis in hepatocellular carcinoma[J].Transl Oncol,2018,11(2):559.
[5]	Tian JP, Zhang J, Zhou JP, et al. Advances in small molecule inhibitors of PD-1/PD-L1 immune checkpoint pathway[J].J China Pharm Univ(中国药科大学学报),2019,50(1):1-10.
[6]	Sharma P,Allison JP.The future of immune checkpoint therapy[J].Science,2015,348(6230):56.
[7]	Zou W,Wolchok JD,Chen L.PD-L1(B7-H1)and PD-1 pathway blockade for cancer therapy:mechanisms,response biomarkers,and combinations[J].Sci Transl Med,2016,8(328):328rv4.
[8]	Greten TF,Xin WW,Korangy F.Current concepts of immune based treatments for patients with HCC:from basic science to novel treatment approaches[J].Gut,2015,64(5):842-848.
[9]	Naidoo J,Page DB,Li BT,et al.Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies[J].Ann Oncol,2015,26(12):2375-2391.
[10]	Zhu H,Bengsch F,Svoronos N,et al.BET bromodomain inhibition promotes anti-tumor immunity by suppressing PD-L1 expression[J].Cell Rep,2016,16(11):2829-2837.
[11]	Jiang Z,Yang Y,Yang Y,et al.Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating PD-L1 and resuming immune[J].Biomed Pharmacother,2017,96:378-383.
[12]	Kim ID,Ha BJ.Paeoniflorin protects RAW 264.7 macrophages from LPS-induced cytotoxicity and genotoxicity[J].Toxicol In Vitro,2009,23(6):1014-1019.
[13]	Liu DF, Wei W, Song LH. Protective effect of paeoniflorin on immunological liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide:modulation of tumour necrosis factor-alpha and interleukin-6 MRNA[J].Clin Exp Pharmacol Physiol,2010,33(4):332-339.
[14]	Lu JT, He W, Song SS, et al. Paeoniflorin inhibited the tumor invasion and metastasis in human hepatocellular carcinoma cells[J].Bratisl Lek Listy,2014,115(7):427-433.
[15]	Hung JY,Yang CJ,Tsai YM,et al.Antiproliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligand-mediated apoptotic pathway in human non-small cell lung cancer A549 cells[J].Clin Exp Pharmacol Physiol,2010,35(2):141-147.
[16]	Xu RX,Nie XH,Jia OY,et al.Paeoniflorin inhibits human glioma cells via STAT3 degradation by the ubiquitin-proteasome pathway[J].Drug Des Devel Ther,2015,9(default):5611-5622.
[17]	Zheng YB,Xiao GC,Tong SL,et al.Paeoniflorin inhibits human gastric carcinoma cell proliferation through up-regulation of microRNA-124 and suppression of PI3K/Akt and STAT3 signaling[J].World J Gastroenterol,2015,21(23):7197-7207.
[18]	Zhao MG,Yang HM,Jiang CH,et al.Intervention effects of the triterpenoids from Cyclocarya paliurus on free fatty acids-induced steatosis in HepG2 cells[J].J China Pharm Univ(中国药科大学学报),2018,49(3):333-340.
[19]	Wang YT,Zhao MG,Sheng XP,et al.Effect of triterpenic acid-enriched fraction from Cyclocarya paliurus on high glucose-induced pancreatic α cells insulin resistance[J].J China Pharm Univ(中国药科大学学报),2018,49(2):215-221.
[20]	Ribas A.Adaptive immune resistance:how cancer protects from immune attack[J].Cancer Discov,2015,5(9):915-919.
[21]	Elkhoueiry AB,Sangro B,Yau T,et al.Nivolumab in patients with advanced hepatocellular carcinoma(CheckMate 040):an open-label,non-comparative,phase 1/2 dose escalation and expansion trial[J].Lancet,2017,389(10088):2492.
[22]	Coombs MR, Harrison ME, Hoskin DW. Apigenin inhibits the inducible expression of programmed death ligand 1 by human and mouse mammary carcinoma cells[J].Cancer Lett,2016,380(2):424-433.
[23]	Hato T,Goyal L,Greten TF,et al.Immune checkpoint blockade in hepatocellular carcinoma:current progress and future directions[J].Hepatology,2014,60(5):1776-1782.
[24]	Abiko K,Matsumura N,Hamanishi J,et al.IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer[J].Br J Cancer,2015,112(9):1501-1509.
[25]	Muhlbauer M,Fleck M,Schutz C,et al.PD-L1 is induced in hepatocytes by viral infection and by interferon-a and-g and mediates T cell apoptosis[J].J Hepatol,2006,45:520-528.
[26]	Yang W,Chen PW,Li H,et al.PD-L1:PD-1 interaction contributes to the functional suppression of T-cell responses to human uveal melanoma cells in vitro[J].Invest Ophthalmol Vis Sci,2008,49(6):2518.
[27]	Niwa Y,Kanda H,Shikauchi Y,et al.Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma[J].Oncogene,2005,24:116-119.
[28]	Timofeeva OA,Tarasova NI,Zhang X,et al.STAT3 suppresses transcription of proapoptotic genes in cancer cells with the involvement of its N-terminal domain[J].Proc Natl Acad Sci U S A,2013,110(4):1267-1272.
[29]	Choudhari S,Khan M,Harris G,et al.Deactivation of Akt and STAT-3 signaling promotes apoptosis,inhibits proliferation and enhances sensitivity of HCC cells to an anti-cancer agent,Atiprimod[J].Mol Cancer Ther,2007,67:2377-2377.
[30]	Chen J,Jiang CC,Jin L,et al.Regulation of PD-L1:a novel role of pro-survival signalling in cancer[J].Ann Oncol,2015,27(3):409-416.

[1]	SHAO Shishuai, DUAN Shukang, TIAN Hong, YAO Wenbing, GAO Xiangdong. Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine[J]. Journal of China Pharmaceutical University, 2023, 54(2): 245-254. DOI: 10.11665/j.issn.1000-5048.2023022803
[2]	YANG Nan, ZHANG Xiao, LYU Hui, HUO Meirong, XU Wei. Advances in immune checkpoint inhibitors combined with other treatments[J]. Journal of China Pharmaceutical University, 2023, 54(2): 131-140. DOI: 10.11665/j.issn.1000-5048.20221028002
[3]	XIA Xuefei, ZHANG Li, LUO Jianhua, YAO Wenbing, GAO Xiangdong, TIAN Hong. Design and antitumor activity of immune checkpoint B7-H3 epitope vaccine[J]. Journal of China Pharmaceutical University, 2021, 52(4): 472-479. DOI: 10.11665/j.issn.1000-5048.20210410
[4]	CHEN Wenting, LIU Jun. Advances in research on immune checkpoint and its inhibitors in glioma[J]. Journal of China Pharmaceutical University, 2021, 52(1): 104-112. DOI: 10.11665/j.issn.1000-5048.20210115
[5]	WANG Ronghua, ZHENG Zhihui, ZHANG Yuqian, MIN Rui, ZHU Ying, ZHANG Pinghu. Progress of research on immune escape mechanism of coronavirus[J]. Journal of China Pharmaceutical University, 2021, 52(1): 1-9. DOI: 10.11665/j.issn.1000-5048.20210101
[6]	CHEN Hongmei, KANG Yanliang, LIU Li, YAO Wenbing, TIAN Hong. Effects of different immunogenic amino acids in PD-L1 vaccine on the differentiation of T cell subsets[J]. Journal of China Pharmaceutical University, 2020, 51(3): 349-356. DOI: 10.11665/j.issn.1000-5048.20200313
[7]	LUO Jianhua, XIA Xuefei, YAO Wenbing, TIAN Hong. Design and antitumor effect of nitrated T helper cell epitope vaccine CD47-NitraTh[J]. Journal of China Pharmaceutical University, 2019, 50(5): 614-621. DOI: 10.11665/j.issn.1000-5048.20190516
[8]	TIAN Jiping, ZHANG Jian, ZHOU Jinpei, ZHANG Huibin. Advances in small molecule inhibitors of PD-1/PD-L1 immune checkpoint pathway[J]. Journal of China Pharmaceutical University, 2019, 50(1): 1-10. DOI: 10.11665/j.issn.1000-5048.20190101
[9]	ZHANG Rui, JIANG Tao, ZENG Tianzhu, YAO Wenbing, GAO Xiangdong, TIAN Hong. Advances of combined immunotherapy in tumor[J]. Journal of China Pharmaceutical University, 2018, 49(4): 383-391. DOI: 10.11665/j.issn.1000-5048.20180401
[10]	CHEN Yali, LI Anqi, ZHANG Ningyue, ZHANG Liang. Purification of monoclonal anti-B7-H4 antibody and the blockade of B7-H4-mediated tumor immune evasion by the antibody[J]. Journal of China Pharmaceutical University, 2017, 48(4): 461-468. DOI: 10.11665/j.issn.1000-5048.20170411

Cited By

Get Citation

PDF

XML

Article views (862) PDF downloads (1043)

Turn off MathJax

Article Contents

Abstract

References

Paeoniflorin inhibits programmed cell death-1-ligand 1 expression in HepG2 cells by regulating JAK/STAT3 signal pathway

Abstract

References

Related Articles

Catalog

Paeoniflorin inhibits programmed cell death-1-ligand 1 expression in HepG2 cells by regulating JAK/STAT3 signal pathway

Abstract

References

Related Articles

Catalog

Export File

Citation

Format

Content