MIF Inhibitor, ISO-1, Attenuates Human Pancreatic Cancer Cell Proliferation, Migration and Invasion in Vitro, and Suppresses Xenograft Tumour Growth in Vivo

Overview

Journal Sci Rep

Specialty Science

Date 2020 Apr 23

PMID 32317702

Citations 14

Authors

Bo Cheng

Qiaofang Wang

Yaodong Song

Yanna Liu

Yanyan Liu

Shujun Yang

Dejian Li

Yan Zhang

Changju Zhu

Affiliations

Soon will be listed here.

Abstract

This study sought to investigate the biological effects of specific MIF inhibitor, ISO-1, on the proliferation, migration and invasion of PANC-1 human pancreatic cells in vitro, and on tumour growth in a xenograft tumour model in vivo. The effect of ISO-1 on PANC-1 cell proliferation was examined using CCK-8 cell proliferation assay. The effect of ISO-1 on collective cell migration and recolonization of PANC-1 cells was evaluated using the cell-wound closure migration assay. The effect of ISO-1 on the migration and invasion of individual PANC-1 cells in a 3-dimensional environment in response to a chemo-attractant was investigated through the use of Transwell migration/invasion assays. Quantitative real time PCR and western blot analyses were employed to investigate the effects of ISO-1 on MIF, NF-κB p65 and TNF-α mRNA and protein expression respectively. Finally, a xenograft tumor model in BALB/c nude mice were used to assess the in vivo effects of ISO-1 on PANC-1-induced tumor growth. We found high expression of MIF in pancreatic cancer tissues. We demonstrated that ISO-1 exerts anti-cancer effects on PANC-1 cell proliferation, migration and invasion in vitro, and inhibited PANC-1 cell-induced tumour growth in xenograft mice in vivo. Our data suggests that ISO-1 and its derivative may have potential therapeutic applications in pancreatic cancer.

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References

Ryan D, Hong T, Bardeesy N . Pancreatic adenocarcinoma. N Engl J Med. 2014; 371(11):1039-49. DOI: 10.1056/NEJMra1404198. View

Manji G, Olive K, Saenger Y, Oberstein P . Current and Emerging Therapies in Metastatic Pancreatic Cancer. Clin Cancer Res. 2017; 23(7):1670-1678. DOI: 10.1158/1078-0432.CCR-16-2319. View

Teague A, Lim K, Wang-Gillam A . Advanced pancreatic adenocarcinoma: a review of current treatment strategies and developing therapies. Ther Adv Med Oncol. 2015; 7(2):68-84. PMC: 4346211. DOI: 10.1177/1758834014564775. View

Siegel R, Ma J, Zou Z, Jemal A . Cancer statistics, 2014. CA Cancer J Clin. 2014; 64(1):9-29. DOI: 10.3322/caac.21208. View

Bloom B, Bennett B . Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science. 1966; 153(3731):80-2. DOI: 10.1126/science.153.3731.80. View

David J . Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci U S A. 1966; 56(1):72-7. PMC: 285677. DOI: 10.1073/pnas.56.1.72. View

Greven D, Leng L, Bucala R . Autoimmune diseases: MIF as a therapeutic target. Expert Opin Ther Targets. 2010; 14(3):253-64. DOI: 10.1517/14728220903551304. View

Adamali H, Armstrong M, McLaughlin A, Cooke G, McKone E, Costello C . Macrophage migration inhibitory factor enzymatic activity, lung inflammation, and cystic fibrosis. Am J Respir Crit Care Med. 2012; 186(2):162-9. PMC: 5448655. DOI: 10.1164/rccm.201110-1864OC. View

Nagarajan P, Tober K, Riggenbach J, Kusewitt D, Lehman A, Sielecki T . MIF antagonist (CPSI-1306) protects against UVB-induced squamous cell carcinoma. Mol Cancer Res. 2014; 12(9):1292-302. PMC: 4284200. DOI: 10.1158/1541-7786.MCR-14-0255-T. View

10.

Oliveira C, de Bock C, Molloy T, Sadeqzadeh E, Geng X, Hersey P . Macrophage migration inhibitory factor engages PI3K/Akt signalling and is a prognostic factor in metastatic melanoma. BMC Cancer. 2014; 14:630. PMC: 4155090. DOI: 10.1186/1471-2407-14-630. View

11.

Liao B, Zhong B, Li Z, Tian X, Li Y, Li B . Macrophage migration inhibitory factor contributes angiogenesis by up-regulating IL-8 and correlates with poor prognosis of patients with primary nasopharyngeal carcinoma. J Surg Oncol. 2010; 102(7):844-51. DOI: 10.1002/jso.21728. View

12.

Suklabaidya S, Das B, Ali S, Jain S, Swaminathan S, Mohanty A . Characterization and use of HapT1-derived homologous tumors as a preclinical model to evaluate therapeutic efficacy of drugs against pancreatic tumor desmoplasia. Oncotarget. 2016; 7(27):41825-41842. PMC: 5173099. DOI: 10.18632/oncotarget.9729. View

13.

Lubetsky J, Dios A, Han J, Aljabari B, Ruzsicska B, Mitchell R . The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents. J Biol Chem. 2002; 277(28):24976-82. DOI: 10.1074/jbc.M203220200. View

14.

Tanese K, Hashimoto Y, Berkova Z, Wang Y, Samaniego F, Lee J . Cell Surface CD74-MIF Interactions Drive Melanoma Survival in Response to Interferon-γ. J Invest Dermatol. 2015; 135(11):2775-2784. PMC: 4640965. DOI: 10.1038/jid.2015.204. View

15.

Schrader J, Deuster O, Rinn B, Schulz M, Kautz A, Dodel R . Restoration of contact inhibition in human glioblastoma cell lines after MIF knockdown. BMC Cancer. 2009; 9:464. PMC: 2810303. DOI: 10.1186/1471-2407-9-464. View

16.

Prabhu L, Mundade R, Korc M, Loehrer P, Lu T . Critical role of NF-κB in pancreatic cancer. Oncotarget. 2014; 5(22):10969-75. PMC: 4294354. DOI: 10.18632/oncotarget.2624. View

17.

Setia S, Nehru B, Sanyal S . Activation of NF-κB: bridging the gap between inflammation and cancer in colitis-mediated colon carcinogenesis. Biomed Pharmacother. 2013; 68(1):119-28. DOI: 10.1016/j.biopha.2013.09.003. View

18.

Shih H, Huang M, Lee C . Polymorphonuclear cell priming associated with NF-kB activation in patients with severe injury is partially dependent on macrophage migration inhibitory factor. J Am Coll Surg. 2010; 211(6):791-7. DOI: 10.1016/j.jamcollsurg.2010.07.028. View

19.

Dessein A, Stechly L, Jonckheere N, Dumont P, Monte D, Leteurtre E . Autocrine induction of invasive and metastatic phenotypes by the MIF-CXCR4 axis in drug-resistant human colon cancer cells. Cancer Res. 2010; 70(11):4644-54. DOI: 10.1158/0008-5472.CAN-09-3828. View

20.

Kamimura A, Kamachi M, Nishihira J, Ogura S, Isobe H, Dosaka-Akita H . Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung. Cancer. 2000; 89(2):334-41. View