| Autor: |
Athanasia Mouzaki, Maria Theodoropoulou, George V.Z. Dedoussis, Alice Maniatis, Andreas Karameris, Marie-Christine Kyrtsonis, Panagiotis G. Menounos |
| Rok vydání: |
1999 |
| Předmět: |
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| Zdroj: |
Experimental Cell Research. 249:269-278 |
| ISSN: |
0014-4827 |
| DOI: |
10.1006/excr.1999.4442 |
| Popis: |
Cisplatin is an effective chemotherapeutic agent that elicits its antineoplastic activity by binding to DNA and disrupting template functions. IL-6 is a cytokine which has been shown to play a central role in host immunological defense mechanisms. Although K562 leukemic cells have been shown to secrete IL-6, little is known of whether there exists a correlation between the expression of IL-6 and the resistance of these cells to anticancer chemotherapeutic agents. To determine the contribution of IL-6 to the regulation of cisplatin-induced apoptosis in K562 cells, we examined whether treatment of K562 cells and cisplatin-resistant K562 subclones with anti-IL-6 mAb enhances their sensitivity to cisplatin. The results show that cis-diamminedichloroplatinum (CDDP) resistance was overcome by treatment with nontoxic doses of CDDP in combination with anti-IL-6 mAb. When we tested if the synergistic effect of anti-IL-6 and cisplatin could restore the ability of K562 mutant cells to undergo apoptosis, we found the typical DNA laddering in these cells, even in the presence of a nontoxic dose of the drug. Treatment of cells with anti-IL-6 reduced the levels of glutathione. The current studies show that anti-IL-6 mAb sensitized CDDP-resistant K562 cells to CDDP by induction of apoptotic death and the reduction of glutathione levels might be implicated in the enhanced cytotoxicity observed. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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