Addition of hTNF alpha potentiates cytotoxicity of taxol in human ovarian cancer lines.
Some reports indicate that the cytotoxic activity of hTNFa and taxol might be enhanced when combined with certain chemotherapeutic agents. To assess if taxol might modulate the action of hTNF alpha, we have studied the cytotoxic action of hTNF alpha in combination with taxol on two ovarian carcinoma cell lines, the SKOV3 and SKVLB. These two cell lines are resistant to the action of hTNF alpha. The SKVLB cells overexpressed the multidrug resistant gene (MDR-1) which confers a resistance to taxol. We observed that the combination of low concentration of hTNF alpha with taxol could increase the cytotoxic activity of taxol in SKOV3 cells. Furthermore, a four-hour pretreatment with taxol before adding hTNF alpha to the culture has shown a significant increase in their cytotoxic activity. This increase was not observed at the same level in SKOV3 cells pretreated with hTNF alpha. However, the phenomena was not observed in SKVLB cells. This indicates that taxol could alter the mechanism of hTNF alpha-resistance.
Berkova
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Laboratoire d'Endocrinologie de la Reproduction, Hospital St-François d'Assise, Québec, Canada.
Pagé
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D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms; D017239:Paclitaxel / Q000633:toxicity*; D011994:Recombinant Proteins / Q000633:toxicity; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D017239:Paclitaxel