Modulation of drug resistance by α-tubulin in paclitaxel-resistant human lung cancer cell lines
| Autor: | E K, Han, E, Kyu-Ho Han, L, Gehrke, S K, Tahir, R B, Credo, S P, Cherian, H, Sham, S H, Rosenberg, S, Ng |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
DNA Complementary Lung Neoplasms Paclitaxel Blotting Western macromolecular substances Drug resistance Biology Transfection DNA Antisense chemistry.chemical_compound Tubulin Sense (molecular biology) Tumor Cells Cultured Humans ATP Binding Cassette Transporter Subfamily B Member 1 Northern blot P-glycoprotein Cell Cycle Blotting Northern Flow Cytometry Antineoplastic Agents Phytogenic respiratory tract diseases Blot Oncology chemistry Drug Resistance Neoplasm Cell culture Immunology biology.protein Cancer research Cell Division |
| Zdroj: | European Journal of Cancer. 36:1565-1571 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/s0959-8049(00)00145-3 |
| Popis: | Beta(beta)-tubulin isotype variation has recently been implicated in the modulation of resistance to paclitaxel in human lung cancer cells and in primary human ovarian tumour samples. Whether alpha-tubulin is involved in drug resistance has not been reported. We have generated a paclitaxel-resistant cell line (H460/T800) from the sensitive human lung carcinoma parental cell line NCI-H460. The resistant cells are more than 1000-fold resistant to taxol and overexpress P-glycoprotein. Interestingly, H460/T800 cells also overexpress alpha- and beta-tubulin as detected by Western blot analysis. From Northern blot analysis, the mechanism of tubulin overexpression appears to be post-transcriptional. To understand whether alpha-tubulin plays a role in drug resistance, we transfected antisense human kalpha1 cDNA construct into the H460/T800 paclitaxel-resistant cells. The antisense clones displayed a reduced alpha-tubulin expression, and the cells were 45-51% more sensitive to paclitaxel and other known antimitotic drugs, compared with vector transfected controls. Complementary experiments of transfecting the sense kalpha1 cDNA into H460 cells conferred a 1.8- to 3.3-fold increase in the IC(50) of several antimitotic agents. Our study suggests that alpha-tubulin is one of the factors that contributes to drug resistance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect