The antiproliferative activity of these hybrids was evaluated on immortalized human keratinocyte (HaCaT) cells stimulated with epidermal growth factor (EGF), an actinic keratosis (AK) model, and on human squamous cell carcinoma (SCC) cells (A431).
Our results showed that EGF‑ETA significantly inhibited the proliferation of EGFR‑positive A431 epidermoid carcinoma (IC50 27 ng/ml) and HN5 head and neck squamous cell carcinoma (IC50 36 ng/ml) cells.
Blocking L-type calcium channel expression or activity using Ca<sup>2+</sup> channel blockers verapamil and diltiazem reduced SCC cell collective invasion both <i>in vitro</i> and <i>in vivo</i> These results identify verapamil and diltiazem, two drugs long used in medical care, as novel therapeutic strategies to block the tumor-promoting activity of the tumor niche.<b>Significance:</b> This work demonstrates that calcium channels blockers verapamil and diltiazem inhibit mechano-sensitization of EGF-dependent cancer cell collective invasion, introducing potential clinical strategies against stromal-dependent collective invasion.<b>Graphical Abstract:</b> http://cancerres.aacrjournals.org/content/canres/78/18/5229/F1.large.jpg <i></i>.
SCC cell lines A-431, Cal-27, and SCC-25 treated with EGF showed a time-dependent increase in ΔNp63α expression at the protein and mRNA levels, which was blocked by the tyrosine kinase inhibitor (TKI) Lapatinib.
Overexpression of the epidermal growth factor (EGF) receptor (EGFR) gene in the squamous cell carcinomas of the head and neck (SCCHN) is often associated with inauspicious prognosis and poor survival.
Our previous studies indicate that epidermal growth factor (EGF)-induced SCC cell proliferation requires the SH3 domain of phospholipase C-γ1 (PLC-γ1), but not its catalytic activity.
Delivery of pSIN-β using the EGF receptor-targeted liposome more effectively controlled the growth of MDA-MB-468 tumors (and human epidermoid carcinoma A431 tumors) in mice than using untargeted liposome.
The loss of HB-EGF in MMP-7-CD44v3 double-positive areas was interpreted to indicate shedding and activation of HB-EGF; this was also detected in Bowen disease indicating its importance in the early phase of SCC development.
However, the integrin becomes phosphorylated by keratinocytes responding to epidermal growth factor in skin wounds or by squamous cell carcinomas that overexpress/hyperactivate the tyrosine kinase ErbB2, epidermal growth factor receptor, or c-Met.
Patients with EGF +61A/A genotype were at risk for squamous cell carcinoma (SCC) (OR 1.70, p = 0.021) and tumor at upper anatomical location (OR 3.11, p = 0.009).
Essential role of c-Jun induction and coactivator p300 in epidermal growth factor-induced gene expression of cyclooxygenase-2 in human epidermoid carcinoma A431 cells.