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.


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.


CONCLUSIONS
This treatment approach may be useful for further development of an effective therapeutic mode for patients with ovarian cancer.
Law
Kim Seng
KS
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan Taiwan, ROC.
Chen
Hung-Chang
HC
Liao
Shuen-Kuei
SK
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020014:K562 Cells; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel