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

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.

A novel mechanism of 6-methoxydihydroavicine in suppressing ovarian carcinoma by disrupting mitochondrial homeostasis and triggering ROS/ MAPK mediated apoptosis

“…Notably, ROS can further trigger the activation of some downstream pro-apoptotic signal pathways, such as the MAPK axis. MAPK has been reported as an important cellular signal transduction molecule that may act as a bridge between ROS and apoptosis in several cancer types (Mao et al, 2008;Dang et al, 2017;Zhu et al, 2017;Lan et al, 2018;Wang et al, 2019;Fontana et al, 2021;Lu et al, 2021;Xing et al, 2021;Li S et al, 2022). Similarly, in our study, we found that 6-ME-caused the activation of JNK/MAPK and ERK/MAPK in OC cells (Figures 5A, B).…”

“…Furthermore, the ERK/ p38-MAPK axis has been linked to ROS-initialed apoptosis caused by liposomal honokiol in medulloblastoma cells . Conversely, the activation of ERK/MAPK may have anti-apoptosis effects in some circumstances (Dang et al, 2017;Lu et al, 2021;Xing et al, 2021). Recent studies have indicated that δ-Tocotrienol increases the sensitivity of OC cells to cisplatin by facilitating the ROS/JNK and ROS/p38 pathways (Fontana et al, 2021).…”

ADAMTS18 deficiency associates extracellular matrix dysfunction with a higher risk of HER2-positive mammary tumorigenesis and metastasis

“…HER2 is mainly involved in RAS-RAF-MEK-ERK pathway for cell proliferation and PI3K-AKT-mTOR pathway for cell survival [ 27 , 28 ]. To determine whether ADAMTS18 deficiency synergistically strengthens the HER2 downstream signaling pathway, we examined the activity of ERK signaling pathway in the mammary epithelium of 30-month-old mice with different genotypes.…”

Ulinastatin ameliorates the malignant progression of prostate cancer cells by blocking the RhoA/ROCK/NLRP3 pathway

“…Currently, the existing documents showed suppressive effects of UTI on the proliferation, motility, and invasion of gastric cancer cells, revealing that UTI could be potentially useful for therapeutic treatment of gastric cancer (J. Wang et al, 2016). Meanwhile, UTI was also regarded as a candidate drug for treating breast cancer, as UTI not only inhibited the proliferation of breast cancer cells, but also enhanced the antitumor effects of chemotherapeutic agents, thereby alleviating tumor growth and metastasis (F. Gao et al, 2013; Xing et al, 2021; Zhong et al, 2012). Currently, more and more research has confirmed the antineoplastic effect of UTI, while its regulatory role in prostate cancer is little studied.…”

“…Recently, the antitumor activity of UTI gradually came to the attention of scholars, and the critical role of UTI in tumor progression has been confirmed in emerging evidence. For instance, UTI inhibits the proliferation and promotes the apoptosis of breast cancer cells by suppressing the ERK signaling pathway (Xing et al, 2021). UTI not only suppresses the proliferation and promotes the apoptosis of liver cancer cells in vitro, but also retards tumor growth in vivo (Song et al, 2015).…”