Non-cytotoxic and sublethal paclitaxel treatment potentiates the sensitivity of cultured ovarian tumor SKOV-3 cells to lysis by lymphokine-activated killer cells

BACKGROUND: The standard treatment of epithelial ovarian cancer is tumor debulking by surgery, followed by six cycles of chemotherapy consisting of cisplatinum and paclitaxel. However, this therapy protocol is not satisfactory, since about 50% of the treated patients eventually experience recurrence within a few years of follow-up. Thus, a more innovative treatment modality is urgently needed for patients with this malignancy. We hypothesized that pretreatment of ovarian cancer SKOV-3 cells at a non-cytotoxic to sublethal dose range of paclitaxel would result in increased sensitivity to LAK-mediated killing. MATERIALS AND METHODS: MTT and trypan blue dye exclusion were used to determine the non-cytotoxic to sublethal range of paclitaxel against SKOV-3 cells. A 4-h 51Cr release cytotoxicity assay was used to evaluate the sensitivity of paclitaxel-treated and untreated SKOV-3 cells. Immunofluorescence/flow cytometric analysis was used for phenotypic changes of cells with or without paclitaxel treatment. RESULTS: Our results with trypan blue dye exclusion and MTT assays showed that the non-cytotoxic to sublethal range was between 0.001 microM and 0.01 microM. Pretreatment of SKOV-3 cells with paclitaxel at these doses for 72 h revealed significantly enhanced LAK-mediated killing against SKOV-3 cells with the highest sensitivity achieved with cells treated with 0.001 microM paclitaxel, as compared with the baseline killing of untreated cells using LAK cell alone (p < 0.05). The enhanced sensitivity of LAK-mediated killing appeared to be in part due to paclitaxel-induced expression of ICAM-1 on SKOV-3 cells. CONCLUSION: This treatment approach may be useful for further development of an effective therapeutic mode for patients with ovarian cancer.