Silencing Smad4 attenuates sensitivity of colorectal cancer cells to cetuximab by promoting epithelial‑mesenchymal transition
| Autor: | Jiantao Zheng, Junfeng Zhou, Lin Zhang, Zhenlv Lin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Epithelial-Mesenchymal Transition Colorectal cancer Cell Cetuximab colorectal cancer Apoptosis Biology Biochemistry 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Cell Movement Cell Line Tumor Genetics medicine Humans Gene silencing Neoplasm Invasiveness Gene Silencing Epithelial–mesenchymal transition Viability assay neoplasms Molecular Biology Smad4 Protein cetuximab resistance Oncogene Articles Cell cycle medicine.disease digestive system diseases Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis embryonic structures Cancer research Molecular Medicine Smad4 Colorectal Neoplasms medicine.drug |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2019.10597 |
| Popis: | The aberrant expression of tumor suppressor Smad4 often occurs in colorectal cancer (CRC), and this phenomenon is believed to be associated with drug resistance. The present study aimed to investigate the effects of Smad4 on the sensitivity of CRC cells to cetuximab, and the possible mechanism underlying such an effect. A total of 629 colorectal adenocarcinoma cases were downloaded from The Cancer Genome Atlas (TCGA) database, and a Smad4 mutation rate of ~21% was demonstrated among the cases. Low expression of Smad4 was present in CRC tissues analyzed by TCGA and in four CRC cell lines, as determined by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis. Cell Counting kit‑8 (CCK‑8) was used to measure the effects of different concentrations of cetuximab on SW480 cell viability at 24 and 48 h. The results demonstrated that treatment of SW480 cells with 20 µg/ml cetuximab for 48 h markedly reduced cell viability. In addition, plasmids were transfected into SW480 cells to induce Smad4 silencing or overexpression. Silencing Smad4 attenuated the sensitivity of SW480 CRC cells to cetuximab; this effect was reflected in increased cell viability and slightly increased migration and invasion, as determined by CCK‑8, wound scratch and Transwell analyses. RT‑qPCR and western blotting was performed to assess the expression levels of apoptosis‑ and epithelial‑mesenchymal transition (EMT)‑related genes. Silencing Smad4 partly reversed the effects of cetuximab on the mRNA and protein expression levels of vimentin, Bax/Bcl‑2 and E‑cadherin. However, Smad4 overexpression enhanced SW480 cell sensitivity to cetuximab. In conclusion, Smad4 may serve a vital role in the sensitivity of CRC cells to chemotherapeutic drugs by promoting EMT. |
| Databáze: | OpenAIRE |
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