KYSE-140

Isoliquiritigenin (ILQ) Inhibited EGFR Activation in ESCC Cells

ESCC is a deadly cancer, rampant in China, linked to high alcohol and tobacco use. EGFR overexpression is noticed in ESCC, associated with tumor aggression. The chalconoid isoliquiritigenin (ILQ) from licorice, known for antioxidative and anticancer effects, is evaluated against ESCC. Ye's team assessed ILQ's antitumor activity through in vitro and in vivo experiments, focusing on its impact on EGFR and downstream signaling pathways (Akt and ERK1/2). The effect of ILQ on EGFR activation was analyzed, showing dose-dependent reduction in EGFR phosphorylation, indicating suppression of EGFR activity (Fig. 1a). This led to decreased phosphorylation of downstream molecules ERK and AKT. After starvation, the phosphorylation of EGFR in ESCC cells (KYSE140, KYSE520, and TE1) was very low, and EGF substantially stimulated the activation of EGFR, but EGF-induced phosphorylation of EGFR was substantially suppressed by ILQ in a dose- and time-dependent manner (Fig. 1b and c). EGFR knockdown using shRNA showed decreased colony formation after ILQ treatment, but cells with reduced EGFR were less sensitive to ILQ, highlighting EGFR pathway inhibition's role in ILQ's antitumor effects (Fig. 1e and f).

Fig. 1. Isoliquiritigenin (ILQ) suppressed EGFR activation in ESCC cells (Ye L, Zhang J, et al., 2020).

KIF23 knockdown inhibited the proliferation of ESCA cells

Esophageal carcinoma (ESCA) is a highly aggressive cancer with low survival rates, largely due to uncontrolled cell proliferation and metastasis, which are often linked to epithelial-mesenchymal transition (EMT). Xu et al. identified differentially expressed DEGs in ESCA from GEO datasets, focusing on KIF23. Expression analysis and functional assays, including cell proliferation tests, are conducted. The expression levels of KIF23 in four ESCA cell lines were measured using qRT-PCR to confirm its upregulation in ESCA. The analysis revealed that Eca-109, KYSE-140, EC9706 and TE-1 cell lines exhibited increased KIF23 mRNA and protein levels when compared to normal cells, with Eca-109 and KYSE-140 showing particularly high levels of expression (Fig. 2A–C). The research team selected these two specific cell lines for additional investigation. Scientists achieved KIF23 knockdown by using si-KIF23 which led to a substantial decrease in protein levels in ESCA cells (Fig. 2D and E). The reduction of ESCA cell proliferation occurred following KIF23 silencing according to results from CCK-8 and EdU assays (Fig. 2F–I). KIF23 inhibition leads to a reduction in ESCA cell growth as shown in Fig. 2F–I.

Fig. 2. Impact of KIF23 knockdown on the proliferation of ESC cells (Xu Q, Li X, et al., 2023).