MIF inhibitor, ISO-1, attenuates human pancreatic cancer cell proliferation, migration and invasion in vitro, and suppresses xenograft tumour growth in vivo

Bo Cheng,Qiaofang Wang,Yanna Liu,Changju Zhu,Dejian Li,Yaodong Song,Yanyan Liu,Yan Zhang,Shujun Yang

doi:10.1038/s41598-020-63778-y

Bo Cheng, Qiaofang Wang + Show 7 more

Open Access

https://doi.org/10.1038/s41598-020-63778-y

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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.

Highlights

This study sought to investigate the biological effects of specific migration inhibitory factor (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
Given that inflammation and immunity are intimately associated with cancer progression, severity and unfavourable prognostic outcomes, it is not surprising that MIF expression have been found to be elevated in numerous cancers including squamous carcinoma, glioblastoma, cervical adenocarcinoma, malignant melanoma, nasopharyngeal cancer, colon cancer, lung cancer, breast cancer, and prostate cancer[17,18,19,20]
The expression of MIF is elevated in human pancreatic cancer tissues

Summary

Introduction

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. 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. Using a in vivo xenograft tumour model in nude mice, we showed that ISO-1 treatment resulted in significant reduction in PANC-1 cell-induced tumour growth with concomitant reduction in MIF expression in tumour tissues. Our findings demonstrates that ISO-1 may offer beneficial effects against pancreatic cancer

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