Effects of Geniposide on the Proliferation, Invasion, and Autophagy of Cervical Cancer Cells by Inhibiting the PI3K/AKT/mTOR Pathway
TIAN Tian1, LI Gang2, ZHANG Feng1, XU Shuna1, LI Weihua1*
This study aims to investigate the effects of GEN (geniposide) on the proliferation, invasion, and autophagy of cervical cancer cells by inhibiting the PI3K (phosphoinositol 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin) pathway. HeLa cells were treated with different concentrations (0, 25, 50, 100 μmol/L) of GEN or with a combination of 100 μmol/L GEN and 10 μmol/L 740Y-P. MTT and colony formation assays were used to detect the effect of GEN on HeLa cell proliferation. Transwell chamber and cell scratch assay were used to detect the effects of GEN on HeLa cell invasion and migration. Flow cytometry was used to detect the effect of GEN on apoptosis of HeLa cells. AO (acridine orange) staining was used to determine the number of AVOs (acidic vesicle organelles) presenting during autophagy. Autophagy of HeLa cells was detected by LC3 immunofluorescence. The mRNA expression levels of PI3K, PTEN, AKT, TSC2 and mTOR in HeLa cells were detected by qRT-PCR. Western blot was used to detect the expression levels of autophagy and PI3K/AKT/mTOR signaling pathway related proteins in HeLa cells. Compared with the GEN-0 group, the survival rate, colony formation number, cell invasion number, migration rate, PI3K, AKT and mTOR mRNA expression, p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR levels of HeLa cells in different concentrations of GEN groups decreased (P<0.05), and the apoptosis rate, AVO quantity, LC3 positive rate, PTEN and TSC2 mRNA expression, Beclin-1 and LC3II/I protein expression increased (P<0.05). Compared with the GEN-100 group, the survival rate and colony formation number, cell invasion number, migration rate, PI3K, AKT and mTOR mRNA expression, p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR levels of HeLa cells in the GEN-100+740Y-P group increased (P<0.05), and the apoptosis rate, AVO quantity, LC3 positive rate, PTEN and TSC2 mRNA expression, Beclin-1 and LC3II/I protein expression decreased (P<0.05). GEN inhibits the PI3K/AKT/mTOR pathway to suppress the proliferation and invasion of cervical cancer cells and promote autophagy.
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EN