TROP2 regulates cisplatin sensitivity of triple-negative breast cancer cells by regulating endoplasmic reticulum stress.

Abstract

Triple-negative breast cancer (TNBC) is a kind of breast cancer with a high metastasis rate and poor prognosis. As a transmembrane glycoprotein, tumor-associated calcium signal transducer 2 (TROP2) plays a certain role in the cancers. This study aimed to explore the potential mechanism of TROP2 affecting cisplatin (CDDP) resistance in TNBC from endoplasmic reticulum stress (ERS). MDA-MB-231 and CDDP-resistant cell lines MDA-MB-231/CDDP were used in this study, and the expression of TROP2 was detected by western blotting. After transfecting with the interference sequence of siRNA targeting TROP2, cell proliferation and apoptosis were detected by the cell counting kit-8, colony formation, and flow cytometry, and the expression of ERS-marker proteins was detected by western blotting. Furthermore, the effects of ERS in TROP2 on drug resistance of TNBC cells were explored by using ERS inhibitor 4-phenylbutyric acid (4-PBA). Results found that TROP2 expression in MDA-MB-231/CDDP was significantly upregulated compared with MDA-MB-231. The expression of TROP2 in MDA-MB-231/CDDP was significantly decreased after transfection with siRNA-TROP2, and the proliferation of MDA-MB-231 and MDA-MB-231/CDDP cells was significantly decreased after further induction with CDDP. TROP2 significantly affected TNBC cell cloning, apoptosis, and the expression of ERS-related marker proteins, while 4-PBA reversed the promoting effects of siRNA-TROP2 on apoptosis and ERS, as well as the inhibitory effects on cell proliferation, suggesting that TROP2 affected the resistance of TNBC cells to CDDP through ERS. In conclusion, TROP2 inhibited apoptosis of TNBC cells, improved the cell cloning ability, and regulated the sensitivity of TNBC cells to CDDP through ERS.