To Define the Attributes of a Novel Theranostic Nanoparticle Dl-N2 to Targeted Integrin Αvβ3 Network in Cholangiocarcinoma(3/3)

pidermal growth factor (EGF) binds with its surface receptors to stimulate gene expression and cancer cell proliferation. EGF stimulated cancer cell growth via PI3K and programmed cell death ligand 1 (PD-L1) pathways. As an integrin αvβ3 antagonist, heteronemin exhibits potent cytotoxic effects in cancer cells. It inhibited critical signal transduction pathways promoted by EGF. In the current study, we investigated EGF-induced signal activation and proliferation effects in cholangiocarcinoma cells and further explored its molecular targets. Heteronemin reversed the effects of EGF and was further enhanced by PI3K activity blockage. Thus, EGF stimulated cell growth in cholangiocarcinoma. Interfering with integrin αvβ3 activities inhibited PI3K activation and PD-L1 expression to reverse the stimulatory effects of EGFinduced gene expression and proliferation in cholangiocarcinoma cells. Xenografted studies also indicated that nano-lipo-drug (DL-N2) inhibited cholangiocarcinoma cancer growth via inhibiting integrin αvβ3 network activities, including EGF-dependent signal
transduction pathways.