Baicalein inhibits cell proliferation and induces apoptosis in glioblastoma by downregulating LGR4-EGFR pathway

Abstract

Abstract Patients with glioblastoma (GBM) have poor prognoses and limited therapeutic options. LGR4 was reported to overexpressed in GBM and involved in tumorigenesis of many cancers, Baicalein (BAI) is a kind of flavonoid that exhibited anti-tumor effects in various tumors. However, the function and association of BAI and LGR4 in GBM are still unclear. In thisi study, firstly, GEPIA and HPA databas was used to perform expression and survival analysis of LGR4 in GBM patients. Then, the significance of LGR4-EGFR in GBM cells (HS683 and KNS89) and GBM animal models was explored by RNA interference and subcutaneous transplantation. Additionally, GBM cells were treated with BAI to explore the role and mechanism of BAI involved in GBM. The results showed that LGR4 was highly expressed in GBM and related to bad prognosis. LGR4 knockdown obviously repressed the proliferation and EGFR expression but induced apoptosis in GBM cells, however, the situations were reserved by EGFR overexpression and CBL knockdown. In contrast, both in vitro and in vivo experiments revealed LGR4 overexpression facilitated GBM cellular biological activities and promoted tumor development, but the effects were rescued by BAI and EGFR inhibitor. In addition, si-LGR4 accelerated EGFR protein degradation while oe-LGR4 exhibit opposite effect. Without affecting normal cellular viability, BAI inhibited malignant behaviour, interacted with LGR4 and blocked the LGR4-EGFR pathway in both GBM cells. Taken together, our data suggested that BAI could inhibit GBM cell proliferation and induce apoptosis via downregulation of the LGR4-EGFR pathway, and the LGR4-EGFR pathway may be an underlying target for GBM therapy of BAI.