Combinational treatment with microRNA-133b and cetuximab has increased inhibitory effects on the growth and invasion of colorectal cancer cells by regulating EGFR

Abstract

Colorectal cancer (CRC) is the third most common cancer with a very poor prognosis predominantly due to its high rate of tumor invasion and migration, and its resistance to anti‑epidermal growth factor receptor (EGFR) therapy. Although CRC has been widely studied, the underlying molecular mechanism remains to be elucidated. MicroRNA (miR)‑133b has been demonstrated to act as a tumor suppressor in several human cancer types by regulating EGFR. However, the detailed involvement of miR‑133b and EGFR in CRC cells remain to be elucidated. The present study used reverse transcription quantitative polymerase chain reaction and characterized the downregulation of the expression levels of miR‑133b in CRC tissues and cell lines. Cell functional assays demonstrated that restored expression of miR‑133b inhibited the growth and invasion of CRC cells. In addition, a luciferase reporter assay revealed that miR‑133b directly targeted EGFR and repressed its expression levels in CRC cells. Additionally, combination treatment with miR‑133b mimics and the monoclonal anti‑EGFR antibody, cetuximab, which is approved and frequently used for treating patients with CRC, exhibited improved inhibitory effects on the growth and invasion of CRC cells compared with treatment with either alone. Taken together, the present study characterized the role of the miR‑133b/EGFR interaction in CRC cells and this suggested the combinational therapy with cetuximab and miR‑133b was positive and may be a potential novel treatment for patients with CRC in the future.

MicroRNAs as Regulators, Biomarkers and Therapeutic Targets in the Drug Resistance of Colorectal Cancer

“…The com- bination of miR-133b mimics with anti-EGFR mAb, exhibited stronger inhibitory effects on CRC cells than treatment with either alone. Thus, the study suggested that miR-133b enhanced the sensitivity to cetuximab, and the combination of miR-133b and cetuximab may be a potential treatment for CRC patients [65]. Similarly, an alike role was found on miR-7.…”

Non-Coding RNAs as Predictive Biomarkers to Current Treatment in Metastatic Colorectal Cancer

“…The authors conclude that reintroduction of miR-143 or miR-145 might lead to resensitize CRC cells to cetuximab by stimulating cetuximab-dependent ADCC to induce cell apoptosis [ 43 ]. The possible interactions among miRNAs and anti-EGFR therapy was revealed also by Zhou et al In this study, combination treatment with miR-133b mimics and cetuximab, exhibited improved inhibitory effects on the growth and invasion of CRC cells compared with treatment with either alone [ 44 ].…”

Negative feedback between TAp63 and Mir-133b mediates colorectal cancer suppression

“…Cell proliferation was determined using the Cell Proliferation Kit I (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) (Sigma, USA) as previously described [14]. Briefly, approximately 1×10 4 cells/well were grown in 96-well plates to 70–80% confluence.…”

“…In gastric cancer, miR-133b acts as a tumor suppressor and negatively regulates FSCN1 expression [13]. Restoring the expression of miR-133b can inhibit the growth and invasion of colorectal cancer cells via directly targeting EGFR [14]. miR-133b can also significantly inhibit bladder cancer cell proliferation and apoptosis by targeting Bcl-w [15].…”