Overcoming Paclitaxel Resistance in Lung Cancer Cells Via Dual Inhibition of Stathmin and Bcl-2
| Autor: | Xiang-Yang Gao, Zheng-Xiang Han, Xiu-Ping Du, Dong-Sheng Pei, Guan Jiang, Hong-mei Wang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Lung Neoplasms Paclitaxel Blotting Western Apoptosis Stathmin Treatment of lung cancer Biology Real-Time Polymerase Chain Reaction Small hairpin RNA chemistry.chemical_compound Downregulation and upregulation Tumor Cells Cultured medicine Humans Radiology Nuclear Medicine and imaging RNA Messenger RNA Small Interfering Lung cancer Cell Proliferation Pharmacology Reverse Transcriptase Polymerase Chain Reaction Antimicrotubule agent Cancer General Medicine medicine.disease Antineoplastic Agents Phytogenic Molecular biology Proto-Oncogene Proteins c-bcl-2 Oncology chemistry Drug Resistance Neoplasm biology.protein Cancer research |
| Zdroj: | Cancer Biotherapy and Radiopharmaceuticals. 28:398-405 |
| ISSN: | 1557-8852 1084-9785 |
| Popis: | Lung cancer is the leading cause of death from malignancy in people and over 85% of these patients eventually die from disseminated disease. Paclitaxel (TAX) is widely used as an antimicrotubule agent for the treatment of lung cancer. Unfortunately, the resistance to this antimicrotubule agent occurs frequently. Stathmin (STMN1) is a ubiquitous microtubule destabilizing protein linked to cancer and cell health and its expression level often correlates with cancer stage progression and prognosis for survival. Overexpression of the antiapoptotic protein Bcl-2 has been shown to prolong drug-induced growth arrest, potentially inducing resistance. In this study, we used a short hairpin RNA (shRNA) approach to evaluate the effect of STMN1 and Bcl-2 downregulation in the sensitivity to TAX in lung cancer cells. We achieved significant downregulation of STMN1 and Bcl-2 mRNA and protein expression by a combination of double shRNA treatment strategy. Our experimental data showed that inhibition of STMN1 and Bcl-2 expression with RNA interference can sensitize lung cancer cells to TAX. These findings suggest a novel approach to improve the efficacy of certain antimicrotubule agents against lung cancer by regulating the function of STMN1 and Bcl-2. |
| Databáze: | OpenAIRE |
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