[Lumican enhanced the therapeutic effect of cisplatin-resistant ovarian cancer by inhibiting the differentiation of Th1 cells].

Objective To investigate the mechanism of the basement membrane proteoglycan lumican (LUM) in cisplatin resistance in ovarian cancer and to preliminarily explore its effect on type 1 T helper (Th1) cell differentiation. Methods Differentially expressed genes (DEGs) between cisplatin-resistant and cisplatin-sensitive ovarian cancer cell lines were screened using the public gene expression database (GEO). The expression levels of these genes were detected by RT-qPCR. LUM expression in human ovarian cancer cells was knocked down using small interfering RNA (siRNA), and the knockdown efficiency was verified by Western blotting. Flow cytometry was used to detect the effects of LUM knockdown on the cell cycle and apoptosis of cisplatin-treated ovarian cancer cell lines. Potential target proteins of LUM were screened through the PPI network, and their interactions were validated by molecular docking. The TIMER database was used to screen the effects of LUM on cytokine secretion in ovarian cancer cell lines, and the results were validated by ELISA and RT-qPCR. Flow cytometry was performed to analyze the regulatory effect of LUM on the differentiation of CD4 T cells. Results GEO data showed that LUM was significantly upregulated in cisplatin-resistant cell lines, and its expression level was correlated with patient prognosis. LUM expression level was higher in that of cisplatin-resistant ovarian cancer cell lines, and cisplatin treatment promoted LUM expression. Knockdown of LUM increased cisplatin-induced apoptosis and cell cycle arrest in ovarian cancer cells, enhancing drug sensitivity. Target gene screening suggested that LUM might regulate cisplatin sensitivity in ovarian cancer cells through interaction with Src homology region phosphatase 2(SHP2). Additionally, TIMER database analysis suggested that high LUM expression inhibited Th1 cell differentiation. Knockdown of LUM in cisplatin-resistant cell lines promoted Th1 cell differentiation by regulating the secretion of interferon γ(IFN-γ) and interleukin 12(IL-12) cytokines, thereby influencing the tumoricidal activity of immune cells. Conclusion LUM is upregulated in cisplatin-resistant ovarian cancer cells and reduces cisplatin sensitivity in ovarian cancer cells by regulating the SHP2-related signaling pathway. LUM also promotes tumor resistance by inhibiting Th1 cell differentiation through the regulation of cytokine secretion by ovarian cancer cells, making it a potential target for ovarian cancer treatment.