Circular RNA CircCDYL Regulates Proliferation and Apoptosis in Non-Small Cell Lung Cancer Cells by Sponging miR-185-5p and Upregulating TNRC6A.

AIM: A series of research reveal that circular RNA (circRNA) plays a vital role in regulating the development of tumor cells. In this research, we would explore the role and mechanism of circCDYL in non-small cell lung cancer (NSCLC). METHODS: RT-PCR was performed to detect the expression of circCDYL in NSCLC tissues, plasma, and cell lines. The tumor cell proliferation ability was evaluated by clone formation assay, and cell cycle determination. Flow cytometry was used to detect apoptosis in NSCLC cell lines. Western blot and RT-PCR were used to assess the expression of proteins and genes. Luciferase assay was performed to confirm the relationship of circRNA-miRNA-mRNA. RESULTS: The decreased level of circCDYL was observed in NSCLC patients' tissues and plasma, which was also downregulated in NSCLC cell lines. Forced expression of circCDYL inhibited cell viability, proliferation and induced apoptosis in A549 cells. Luciferase assay verified that circCDYL could bind with miR-185-5p and confirmed that TNRC6A was a downstream target of miR-185-5p. Overexpression of miR-185-5p or silencing of TNRC6A could inhibit the anti-tumor effect of circCDYL in A549 cells via regulating the ERK1/2 signal. CONCLUSION: Here, we revealed that circCDYL inhibited proliferation and induced apoptosis in NSCLC cell lines via regulating ERK1/2 signal, and the mechanism of this progression may target miR-185-5p/TNRC6A, which provided a theoretical basis for clinical therapy.

The effect of monoclonal antibody cetuximab (C225) in combination with tyrosine kinase inhibitor gefitinib (ZD1839) on colon cancer cell lines.

AIMS: The epidermal growth factor receptor (EGFR) is abnormally activated in many tumours. Two different categories of compounds targeting EGFR, monoclonal antibodies (mAbs) and low molecular weight tyrosine kinase inhibitors (TKIs), which target extracellular and intracellular domains of the receptor, respectively, have shown antitumour activity. We decided to explore whether the combined administration of cetuximab, a mAb, and gefitinib, a TKI, had superior antitumour activity than either agent given alone. METHODS: We studied the effects of cetuximab alone, gefitinib alone and the combination of cetuximab and gefitinib in two colon cancer cell lines, HT-29 and LoVo. The effects of these two agents on cell proliferation and induction of apoptosis were evaluated. RESULTS: Dose-dependent activity of cetuximab alone or gefitinib alone or the combination was observed for both colon cancer cell lines. In addition, the combined treatment with cetuximab and gefitinib resulted in a synergistic and more pronounced growth effect on cell proliferation and induction of apoptosis than either single-agent treatment. CONCLUSIONS: Our findings suggest that combined treatment with distinct EGFR inhibitory agents can augment the antitumour response over that realised with a single EGFR inhibitor. New and tempting treatment strategies on the EGFR target consisting of a double hit with a mAb and a TKI may improve the therapeutic ratio for colorectal cancer in future clinical trials.