Small interfering RNA targeting epidermal growth factor receptor enhances chemosensitivity to cisplatin, 5‐fluorouracil and docetaxel in head and neck squamous cell carcinoma

Abstract

Overexpression of epidermal growth factor receptor (EGFR) has been found in various epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC), and is associated with increased tumor growth, metastasis, resistance to chemotherapeutic agents and poor prognosis. As such, EGFR is a potential target for antitumor therapy and several EGFR inhibitors have been investigated in preclinical or clinical settings. In the present study, we used small interfering RNA (siRNA) to downregulate EGFR expression while evaluating the effect of EGFR siRNA on cell proliferation, and the combined effects with cisplatin, 5-fluorouracil (5-FU) and docetaxel in HNSCC. Furthermore, HNSCC xenografts were treated with EGFR siRNA alone or in combination with cisplatin, and tumor growth was examined. EGFR expression, proliferation, angiogenesis and apoptosis index were evaluated by immunohistochemistry. The results showed that EGFR siRNA efficiently downregulated EGFR expression and inhibited cell growth of HNSCC. Treatment with EGFR siRNA in combination with cisplatin, 5-FU and docetaxel enhanced chemosensitivity with a significant increase in apoptosis. EGFR siRNA delivered by atelocollagen enhanced the antitumor effect of cisplatin in the HNSCC xenograft model. These cumulative results suggest that EGFR siRNA combined with cisplatin, 5-FU and docetaxel may be a feasible strategy to enhance the effects of chemotherapy in patients with HNSCC.

XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth

“…To evaluate the proliferation index, Ki-67-stained cells were quantified in five randomly selected fields at 400ϫ magnification. The percentage of cells that showed positive nuclear staining for the Ki-67 antigen was considered to be the proliferation index, 17 which was calculated by analyzing five different tumors from each group.…”

“…All slides were subjected to identical exposure times. For an evaluation of the apoptotic index in each section, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL)-stained cells were quantified in five randomly selected fields at 400ϫ magnification, and the apoptotic index was calculated as the number of positive cells/total number of cells ϫ 100%, 17 from five tumors per group.…”

RNAi-mediated knockdown of AURKB and EGFR shows enhanced therapeutic efficacy in prostate tumor regression

“…Most current cancer treatments are combinations of chemotherapeutic agents, and it is expected that newer targeted drugs achieve their greatest efficacy in combination with traditional cytotoxic agents. Recently, a number of studies 10,11,15 explored the possibility of combining relatively specific drug molecules (tyrosine kinase inhibitors) with traditional chemotherapeutic agents (Taxanes, platinum, etc.) to sensitize the cancer cells toward chemotherapeutic drugs enhancing, cytotoxic properties.…”

Studies on the inhibition of feline EGFR in squamous cell carcinoma: Enhancement of radiosensitivity and rescue of resistance to small molecule inhibitors

“…24 RNA interference techniques are extensively used in research but also carry promise for the development of drugs capable of targeting specific proteins 25,26 including EGFR. 27 The aims of this study were to investigate the role of EGFR in feline SCCs. Initial results supported the use of small molecule TKI in these tumors, but resistance to therapy developed.…”