α2A-Adrenergic Receptor Inhibits the Progression of Cervical Cancer Through Blocking PI3K/AKT/mTOR Pathway

OBJECTIVE: The study aimed to investigate the effect of α2A-adrenergic receptor (ADRA2A) on cervical cancer and the potential mechanisms of ADRA2A on phosphatidylinositol 3′-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in cervical cancer cells. METHODS: In our study, ADRA2A expression was evaluated by analyzing cervical cancer RNA sequencing dataset from the GEPIA. The prognostic values of ADRA2A were evaluated by Kaplan–Meier method using the Cancer Genome Atlas (TCGA) database data. In addition, the expression of ADRA2A in cervical cancer cell lines was detected by qRT-PCR and Western blot. Subsequently, the roles of ADRA2A on cell proliferation, apoptosis, migration, invasion and senescence in HeLa and SiHa cells were evaluated. Moreover, tumorigenesis in nude mice was used to investigate the role of ADRA2A in vivo. We also detected the expression changes of key factors in PI3K/Akt/mTOR pathway after overexpression and silencing of ADRA2A in HeLa and SiHa cells. RESULTS: ADRA2A expression was significantly downregulated in cervical cancer tissues and cell lines. The high expression of ADRA2A was significantly associated with a better prognosis in cervical cancer patients. ADRA2A overexpression significantly suppressed cell proliferation, migration and invasion, and promoted cell senescence and apoptosis in cervical cancer cells. On the contrary, silencing ADRA2A dramatically facilitated cell proliferation, migration and invasion, and inhibited cell senescence and apoptosis in cervical cancer cells. The expressions of p-PI3K, p-AKT and p-mTOR in cervical cancer cells were notably decreased by ADRA2A overexpression and increased by silencing ADRA2A. In addition, we also confirmed that ADRA2A overexpression could suppress the xenograft tumor growth in vivo. CONCLUSION: Our study demonstrated that ADRA2A could suppress cell proliferation, migration and invasion, as well as promote cell senescence and apoptosis through inhibiting PI3K/Akt/mTOR pathway in cervical cancer.