β-elemene inhibits bladder cancer cell through the expression of cell membrane protein GM3

Abstract

BACKGROUND

Β-elemene is widely used to treat a variety of cancers, including bladder cancer (BLCA). However, the anti-cancer target, effective constituents and mechanism was unclear.

AIM

To investigate the therapeutic effect and underlying mechanism of β-elemene in BLCA.

METHODS

We first mined the GEPIA2 database to explore the association between the GM3 (ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5, GM3, ST3GAL5) gene and BLCA. Second, we performed in vitro experiments using BLCA cells to verify the inhibitory effect and targets therapy of β-elemene on BLCA.

RESULTS

Our results revealed a significantly reduced expression of GM3 in BLCA tissues. Notably, BLCA patients with higher GM3 expression exhibited prolonged overall survival and disease-free survival. In vitro studies demonstrated that β-elemene significantly affected BLCA cell viability, leading to a marked upregulation of GM3 expression, increased apoptotic cell populations, and a notable reduction in cell migration and invasion. WB analysis showed that β-elemene enhanced GM3 protein expression while simultaneously decreasing phosphorylated epidermal growth factor receptor (p-EGFR) levels. Additionally, overexpression or RNAi of GM3 in BLCA cells resulted in corresponding changes in epidermal growth factor receptor and p-EGFR expression levels.

CONCLUSION

This study provides preliminary evidence for further investigation into the molecular mechanisms of β-elemene in the treatment of BLCA.

Keywords: Β-elemene; Bladder cancer; EGFR; GM3; Malignancy

Core Tip: We believe that our study makes a significant contribution to the literature because GEPIA2 database deep mining revealed that GM3 was poorly expressed in bladder cancer (BLCA), and this study showed that β-elemene inhibited BLCA cells by increasing GM3 expression. Moreover, cluster analysis showed that GM3 increased cell adhesion and inhibited the invasion and migration of BLCA cells by expressing membrane-related signaling proteins. Further, we believe that this paper will be of interest to the readership of your journal because the use of β-elemene in anti-cancer medication is advantageous owing to its significant anti-tumor activity against various types of cancer and its reduced toxicity, which ensures that its impact on the quality of life of patients with cancer is minimal and the drug is well tolerated. Thus, this study provides a preliminary basis and strong evidence for further research on the underlying molecular mechanisms of β-elemene in the treatment of BLCA.