A linear polyethylenimine mediated siRNA-based therapy targeting human epidermal growth factor receptor in SPC-A1 xenograft mice.

Abstract

Background: Linear polyethylenimine (LPEI) is considered as a desirable gene in vivo delivery system, but whether it could deliver the specific siRNA targeted EGFR to the tumor site to inhibit the growth of NSCLC xenograft in nude mice still needs to be examined.

Methods: In this study, LPEI/siRNA was made into a complex and SPC-A1-xenografted mice model was established. Then, stable LPEI/siRNA-EGFR complexes were intraperitoneally administrated. Afterwards, tumor growth was measured every 3 days. At the end of the experiment, tumor volume was calculated, and tumors were weighed, and examined for EGFR expression, proliferation, and apoptosis evaluations. By using blood samples, toxicity tests including aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine (Cr) were measured for liver and renal function evaluation. Serum concentrations of TNF-α and IFN-γ were also examined.

Results: Our results demonstrated that LPEI/siRNA-EGFR complexes could downregulate EGFR expression in SPC-A1 xenografted tumor upon single i.p. injection. LPEI/siRNA-EGFR complexes inhibited tumor growth and did not induce organ toxicity in SPC-A1-xenografted mice. At the end of the experiment no significant IFN-α increase was detected in LPEI/siRNA complexes or glucose-treated groups.

Conclusions: The novel modality of siRNA-based therapy targeting EGFR may be of great potential in NSCLC treatment.