PURPOSE: Some inhibitors of Epidermal-Growth-Factor-receptor (EGFR) are FDA approved for clinical use against non-small-cell-lung-cancer(NSCLC) while more are in bench-research and clinical-trial stages. Data on the role of EGFR targetted therapy on Small-Cell-Lung-Cancer (SCLC) is limited. We studied the effect of a novel endogenous peptide, ERRP(EGF Receptor related Peptide), on in-vitro proliferation of SCLC and NSCLC cell-lines.
METHODS: Human NSCLC cell-line NCI-H522 and differential HER-expressing Human SCLC cell line NCI-H526, NCI-H69 and NCI-H146 were cultured in RPMI/10% fetal-bovine-serum/pen-strep media. 5000 Cells were plated in 96-well plates,incubated for 48 hours, washed in PBS, and subsequently incubated for 48 more hours in low-serum medium containing different dose of ERRP. Cells were then incubated with MTT (1 mg/mL) at 37°C for 2 hours and then with DMSO at room temperature for 1 hour. Spectrophotometric absorbance of the samples was determined by Microplate Reader. Results were plotted as means ± SD of three separate experiments having six determinations per experiment for each experimental condition.Western blot analysis was done to study comparatie HER receptor expression.
RESULTS: After analysis of MTT assay cell viability data, it was shown that there was a dose dependent inhibition of proliferation of the NSCLC as well all the three SCLC cell lines after they were exposed to ERRP for 48 hours. In case of NSCLC NCI H522 cell lines, the there was a drop of 30%, 60% and 80% respectively with 2.5 ug/ml, 5 ug/ml and 10 ug/ml dose of ERRP. There were almost identical rates of decrease in viable cells in plates containing SCLC cell lines NCI H69, NCI H146 and NCI H526 cell lines.
CONCLUSION: The ERRP-induced decrease in number of cells is due to inhibition of cell proliferation. This has been confirmed in earlier studies on EGFR-free Fibroblast cells. Our data shows that ERRP has significant inhibitory effect on SCLC-cell-lines irrespective of EGFR-expression. The degree of inhibition was nearly identical to that on NSCLC-cell-lines.
CLINICAL IMPLICATIONS: Addition of EGFR-inhibiting-agents as therapeutic option against SCLC has potential for improving Small-Cell-Lung-Cancer-mortality.
DISCLOSURE: Ahmed Khan, No Financial Disclosure Information; No Product/Research Disclosure Information