Genistein inhibits migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways

Abstract

ObjectiveGenistein obviously inhibits the migration and invasion of various tumor cells. However, its effects on cervical cancer cells have seldom been referred. We aimed to evaluate the effects of genistein on the proliferation, migration and invasion of cervical cancer HeLa cells, the expressions and phosphorylations of proteins related with FAK-paxillin and MAPKs signaling pathways, as well as the expressions of related key genes. Materials and methodsHeLa cells were stimulated with genistein for 24 h and 48 h respectively. After adherence for 2 h, 0 μM, 12.5 μM, 25 μM, 50 μM and 100 μM genistein solutions were added in DMEM. Cell proliferation was tested by the CCK-8 assay. After treatment with 100 μM genistein, the migration ability was detected by the scratch assay. Transwell assay was used to detect cell migration and invasion abilities. Western blot and qRT-PCR were used to detect the expressions of proteins and mRNAs related with FAK-paxillin and MAPKs signaling pathways respectively. ResultsThe effect of genistein on the proliferation of HeLa cells was proportional to treatment time and drug dose, and the proliferation was inhibited after 24 h and 48 h at 100 μM. After treatment with 100 μM genistein, the scratch migration rate was significantly lower than that of the control group at 24 h and 48 h (P < 0.05). Genistein also inhibited the invasion of tumor cells through the upper chamber and Matrigel. The number of invasive cells was significantly lower than that of the control group (P < 0.05). Genistein significantly inhibited the phosphorylations of FAK, paxillin, p38 and p42/44. Compared to the control group, 100 μM genistein significantly suppressed the mRNA expressions of FAK, paxillin, Snail and twist. ConclusionGenistein inhibited the migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways in dose-dependent manners.