Effects of Ulinastatin on Proliferation and Apoptosis of Breast Cancer Cells by Inhibiting the ERK Signaling Pathway.

Xin Wang,Zeyu Xing,Junyan Liu,Jiaqi Liu,Xiang Wang,Menglu Zhang,Kexin Feng,Gang Liu

doi:10.1155/2021/9999268

Abstract

Purpose To explore the effects of ulinastatin on the proliferation and apoptosis of breast cancer cells and the relevant mechanism of action. Methods Breast cancer cells (MCF-7) were cultured and randomly divided into three groups, namely, control group, ulinastatin group, and ulinastatin+extracellular-regulated protein kinase (ERK) inhibitor group. Then, the Cell Counting Kit-8 (CCK-8) assay was carried out to detect the effect of ulinastatin on the viability of breast cancer cells. The effects of ulinastatin on the proliferation and apoptosis of breast cancer cells were determined via EdU staining and Hoechst 33258 staining assays, respectively. The messenger ribonucleic acid (mRNA) and protein expression levels of ERK and forkhead box O3 (FOXO3) in breast cancer cells were measured through reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Results In comparison with the control group, the ulinastatin group displayed decreased viability of breast cancer cells, a decreased positive rate of 5-ethynyl-2′-deoxyuridine (EdU) staining, an increased positive rate of Hoechst 33258 staining, and reduced mRNA and protein levels of ERK and FOXO3 in breast cancer cells. Compared with those in the ulinastatin group, the viability of breast cancer cells was lowered, the positive rate of EdU staining was reduced, the positive rate of Hoechst 33258 staining was raised, and the mRNA and protein levels of ERK and FOXO3 in breast cancer cells clearly declined in the ulinastatin+ERK inhibitor group. Conclusion Ulinastatin inhibits the proliferation and promotes the apoptosis of breast cancer cells. The possible mechanism of action is associated with the suppression of the ERK signaling pathway.

Highlights

Breast cancer, one of the most common malignancies among women in China and even in the world at present, has become the leading killer threatening the health of women, which accounts for about 20% of malignant tumors among women [1]
800 U/mL ulinastatin was given in the ulinastatin group, while 800 U/mL ulinastatin and 500 nM extracellular-regulated protein kinase (ERK) inhibitor solution were given in the ulinastatin+ERK inhibitor group
The results of the Cell Counting Kit-8 (CCK-8) assay shown in Figure 1 revealed that compared with that in the control group, the viability of breast cancer cells decreased significantly in the ulinastatin group at 24 h, 48 h, and 72 h (∗p < 0:05, ∗p < 0:05, and ∗p < 0:05), while it was overtly lower in the ulinastatin+ERK inhibitor group than in the ulinastatin group (#p < 0:05, #p < 0:05, and #p < 0:05), indicating that ulinastatin represses the viability of breast cancer cells, and the inhibitory effect is more obvious after using the ERK inhibitor

Summary

Introduction

One of the most common malignancies among women in China and even in the world at present, has become the leading killer threatening the health of women, which accounts for about 20% of malignant tumors among women [1]. Reports of the World Health Organization have stated that about 1.5 million people suffer from breast cancer every year worldwide, and about 500,000 patients with breast cancer die. With continuous improvement and perfection of modern medicine, certain progress has been made in the prevention and treatment of breast cancer, mainly including chemoradiotherapy, surgery, or endocrine therapy [4]. Medical practitioners apply some targeted inhibitors in clinical treatment, but the efficacy is unsatisfactory. Further investigating the pathogenesis of breast cancer and finding out drugs preventing or treating breast cancer are major issues to be solved

Methods

Results

Conclusion