Abstract
BackgroundNon-small-cell lung carcinomas (NSCLCs) exhibit poor prognosis and are usually resistant to conventional chemotherapy. Absence of p21WAF1/CIP1, a cyclin-dependent kinase (cdk) inhibitor, has been linked to drug resistance in many in vitro cellular models. RNA activation (RNAa) is a transcriptional activation phenomena guided by double-strand RNA (dsRNA) targeting promoter region of target gene.MethodsIn this study, we explored the effect of up-regulation of p21 gene expression on drug-resistance in A549 non-small-cell lung carcinoma cells by transfecting the dsRNA targeting the promoter region of p21 into A549 cells.ResultsEnhanced p21 expression was observed in A549 cells after transfection of dsRNA, which was correlated with a significant growth inhibition and enhancement of chemosensitivity to cisplatin in A549 cells in vitro. Moreover, in vivo experiment showed that saRNA targeting the promoter region of p21 could significantly inhibit A549 xenograft tumor growth.ConclusionsThese results indicate that p21 plays a role in lung cancer drug-resistance process. In addition, this study also provides evidence for the usage of saRNA as a therapeutic option for up-regulating lower-expression genes in lung cancer.
Highlights
Non-small-cell lung carcinomas (NSCLCs) exhibit poor prognosis and are usually resistant to conventional chemotherapy
Lung carcinoma cell proliferation and colony formation were inhibited by p21 up-regulation in vitro An important characteristic of tumor cells is their increased proliferative capability, which is often caused by impaired regulation of the cell cycle
It has been reported that p21 can regulate the cell cycle process by binding and inhibiting cyclin-dependent kinases, so we examined the effect of p21 transcriptional activation on the proliferation of A549 cells in vitro
Summary
Non-small-cell lung carcinomas (NSCLCs) exhibit poor prognosis and are usually resistant to conventional chemotherapy. Absence of p21WAF1/CIP1, a cyclin-dependent kinase (cdk) inhibitor, has been linked to drug resistance in many in vitro cellular models. Lung cancer is the most common cause of cancer mortality worldwide. Non-small-cell lung carcinomas (NSCLCs), which represent around 80% of lung tumors, exhibit poor prognosis and are usually resistant to conventional chemotherapy. Cisplatin is one of the most potent anticancer agents, displaying significant clinical activity against a variety of solid tumors. The most effective systemic chemotherapy for non-small cell lung cancer (NSCLC) was cisplatin-based combination treatment. The outcome of cisplatin therapy on NSCLC seems to be unsatisfactory. The use of cisplatin in cancer chemotherapy is limited by acquired or intrinsic resistance of cells to the drug. The cytotoxicity of cisplatin is believed mainly due to interaction with
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