| Paclitaxel (Taxol) is a new generation of chemotherapy drugs against several types of malignant tumors. Although the primary mechanism of action of paclitaxel is attributed to its ability to bind microtubules, its efficacy exceeds that of conventional microtubule-disrupting agents, suggesting that paclitaxel may have additional cellular effects. In order to investigate the effects of paclitaxel, we tested the expression of specific genes in cancer cells treated with paclitaxel. We found that paclitaxel can induce IL-8 gene transcription in subsets of human ovarian cancer cell lines. This induction does not appear to be linked to the LPS (lipopolysaccharide) pathway of IL-8 gene induction. We then identified the AP-1 and NF-;To further study the role of IL-8 in mediating the effects of paclitaxel as well as understanding the biological significance of this specific chemokine, the human IL-8 gene was transfected into IL-8 non-producing human ovarian cancer cell lines. The transfected cells or controls were injected into nude mice to test the in vivo effects of IL-8. The production of hu-IL-8 dramatically suppressed tumor growth in nude mice. Histological analysis of tumors at the site injection showed marked infiltration of immune cells. These results suggest that IL-8 induction by tumor cells may be beneficial to the host by attracting immune cells to the tumor site. |
