| MyD88 expression and anti-apoptotic signals of paclitaxel in epithelial ovarian cancer cells. |
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Dong Soo Suh, Moo Sung Jo, Shin Ae Yu, Ki Hyung Kim, Man Soo Yoon |
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Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, Korea. ghkim@pusan.ac.kr |
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| Abstract |
OBJECTIVE
The objectives of this study was to evaluate the correlation between myeloid differentiation protein 88 (MyD88) expression and paclitaxel effects on epithelial ovarian cancer cells and to evaluate whether paclitaxel had anti-apoptotic signals. METHODS: Epithelial ovarian cancer cells isolated from ascites and established cell lines were treated with increasing concentrations of paclitaxel (0.2 to 20 microM) for 24 and 48 hours and cell viability was determined using the CellTiter 96 AQueous One Solution Cell Proliferation Assay. Cytokine profiling was performed from culture supernatants using the Luminex 200 system. Nuclear factor-kappaB (NF-kappaB) activity was determined using a Luciferase reporter system. Levels of phospho-extracellular signal-regulated kinase (p-ERK) were measured by Western blot analysis. RESULTS: A strong signal for MyD88 expression was observed in R182, 01-19b and SKOV3 cells (MyD88-positive). A2780, R454 and 01-28 cells showed low levels of MyD88 (MyD88-negative). Paclitaxel effectively decreased cell viability in MyD88-negative A2780, R454, 01-28 cells after 24 and 48 hours (57%, 49%, 42% and 35%, 28%, 29%, respectively). MyD88-positive cells were resistant to paclitaxel. There was a significant increase in caspase-3/7 activity following paclitaxel treatment in MyD88-negative cells. No significant change in caspase-3/7 activity was detected in MyD88-positive cells. Paclitaxel induced NF-kappaB activation and enhanced the secretion of interleukin-6 (IL-6) and IL-8 in a dose dependent manner and induced ERK phosphorylation on MyD88-positive cells. CONCLUSION: Paclitaxel treatment for MyD88-positive ovarian cancer could have detrimental effects due to the paclitaxel-induced enhancement of NF-kappaB, ERK activities and pro-inflammatory cytokine production, which promote chemoresistance and tumor progression. |
| Key Words:
Paclitaxel, Myeloid differentiation factor 88, Ovarian neoplasms, Anti-apoptotic |
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