Gefitinib induces anoikis in cervical cancer cells
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Gefitinib exerts anticancer effects on various types of cancer,such as lung, ovarian, breast, and colon cancers. However, thetherapeutic effects of gefitinib on cervical cancer and the underlying mechanisms remain unclear. Thus, this study aimedto explore whether gefitinib can be used to treat cervical cancerand elucidate the underlying mechanisms. Results showed thatgefitinib induced a caspase-dependent apoptosis of HeLa cells,which consequently became round and detached from thesurface of the culture plate. Gefitinib induced the reorganization of actin cytoskeleton and downregulated the expression ofp-FAK, integrin β1 and E-cadherin, which are important in cellextracellular matrix adhesion and cell-cell interaction, respectively. Moreover, gefitinib hindered cell reattachment and spreading and suppressed interactions between detached cells insuspension, leading to poly (ADP-ribose) polymerase cleavage,a hallmark of apoptosis. It also induced detachment-inducedapoptosis (anoikis) in C33A cells, another cervical cancer cellline. Taken together, these results suggest that gefitinib triggersanoikis in cervical cancer cells. Our findings may serve as abasis for broadening the range of anticancer drugs used to treatcervical cancer.
Abstract
Gefitinib exerts anticancer effects on various types of cancer,such as lung, ovarian, breast, and colon cancers. However, thetherapeutic effects of gefitinib on cervical cancer and the underlying mechanisms remain unclear. Thus, this study aimedto explore whether gefitinib can be used to treat cervical cancerand elucidate the underlying mechanisms. Results showed thatgefitinib induced a caspase-dependent apoptosis of HeLa cells,which consequently became round and detached from thesurface of the culture plate. Gefitinib induced the reorganization of actin cytoskeleton and downregulated the expression ofp-FAK, integrin β1 and E-cadherin, which are important in cellextracellular matrix adhesion and cell-cell interaction, respectively. Moreover, gefitinib hindered cell reattachment and spreading and suppressed interactions between detached cells insuspension, leading to poly (ADP-ribose) polymerase cleavage,a hallmark of apoptosis. It also induced detachment-inducedapoptosis (anoikis) in C33A cells, another cervical cancer cellline. Taken together, these results suggest that gefitinib triggersanoikis in cervical cancer cells. Our findings may serve as abasis for broadening the range of anticancer drugs used to treatcervical cancer.
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