Fig. 4

Immunohistochemical expression of PCNA and Ki67 in tumor tissue sections isolated from treated animals. a, b Untreated tumors cells expressing PCNA and Ki67 proteins indicating their cycling status, while PEG-AuNSs seems to induce a minimal inhibition to PCNA and Ki67 proteins. c-h FGFR1i- CPT- and 5Fu- AuNSs induced a significant inhibition to PCNA and Ki67 activity compared with the free form. i, j Bar chart plots of the average tissue section area showing positive immunoreaction for both PCNA and Ki67 normalized to the total area. The drugs and their corresponding nanoconjugates resulted in significant lack of proliferation of the tumor cells compared with untreated and PEG-AuNSs treated cells. There was no significance difference between the inhibitory effect induced by CPT, 5Fu and EGFRi (denoted by ns). Also, the same drug nanoconjugates appear to induce equivalent rates of cellular arrest. PCNA and Ki67 immunoreactions were significantly lower in tumor cells treated with FGFR1i- CPT- and 5Fu- AuNSs compared with the free forms. Findings were considered statistically significant when p< 0.001 and are denoted by asterisks. Scale bars=100 um (n= 13)