목적: 상피성 난소암 세포주 및 정상 상피성 난소 세포주에서 외인성, 내인성 Osteopontin이 세포 성장에 미치는 영향을 비교하며 상피성 난소암세포주의 paclitaxel 감수성에 미치는 영향을 알아본다. 연구 방법: 상피성 난소암 세포주 중 내인성 osteopontin이 적게 발현되고 paclitaxel에 감수성이 높은 OV429와 높게 발현되고 내성을 보이는 OV420, 그리고 정상 난소의 상피 세포에 정제된 Osteopontin을 처치하여 각각의 세포주에서 가장 높은 감수성을 보이는 Osteopontin의 농도 및 증식정도를 비교한다. 또한 OV420 세포주에서 osteopontin siRNA를 처리한 후 처리 전 후의 증식의 변화와 paclitaxel에 대한 감수성의 변화를 비교하여 내인성 osteopontin이 상피성 난소암 세포주에서의 역할을 확인한다. 각각에서 증식정도 및 세포주기의 변화는 Tetrazolium colorimetric (XTT) assay 및 FACS analysis를 이용하여 시행하였다. 결과: 내인성osteopontin이 적게 발현되는 OV429 세포주에서 정제된 osteopontin은 증식을 촉진시키나 (P<0.05), 정상 세포주에서는 증식의 변화를 볼 수 없었다. 또한 내인성 osteopontin이 높게 발현되는 OV420 세포주에 osteopontin siRNA를 처리하면 증식이 현저히 억제되며 (P<0.05), G2/M기에 정체되었고 osteopontin siRNA를 처리한 후 paclitaxel을 처치한 경우, osteopontin siRNA처리 전에 비하여 세포들의 군집이 억제되며 약제 감수성이 증가하여 생존률의 현저한 감소를 보였다 (P<0.05). 결론: 외인성 osteopontin은 상피성 난소암 세포주에서 증식을 촉진시키나 정상세포에서는 그 작용이 미비하며 내인성 osteopontin은 상피성 난소암 세포주에서 paclitaxel의 감수성 억제와 밀접한 관련을 보이는데 이는 세포의 군집 여부와 관련이 있는 것으로 추정된다.

Objective: To evaluate the effects of both exogenous and endogenous osteopontin on normal and malignant ovarian epithelial cell growth, and on paclitaxel chemo-resistance. Methods: The ovarian cancer cell line OV429, which showed low level of endogenous osteopontin and paclitaxel sensitive cell line OV420, which showed high level of endogenous osteopontin, and a normal ovarian epithelial (HOSE: Human ovarian surface epithelial) cells were treated with purified osteopontin. Furthermore, OV420 was treated with osteopontin siRNA alone or in combination with paclitaxel. Proliferation rates and cell cycle progression of treated cells were determined by the tetrazolium colorimetric (XTT) assay and FACS analysis, respectively. Results: Exogenous osteopontin increased the proliferation rate of OV429 and OV420 but had negligible effect on normal HOSE. Ovarian cancer cell lines treated with siRNA showed significantly reduced the growth rates (P<0.05), and they were arrested in G2/M phase of the cell cycle. Furthermore, OV420 treated with paclitaxel in the presence of osteopontin siRNA showed significantly decreased the survival rate. Conclusion: Osteopontin promote cell growth in malignant but not in normal ovarian epithelial cells, and may confer paclitaxel-resistance by adhesion to each cell and minimized the cell surface which exposure to chemo-agents.

Objective: To evaluate the effects of both exogenous and endogenous osteopontin on normal and malignant ovarian epithelial cell growth, and on paclitaxel chemo-resistance. Methods: The ovarian cancer cell line OV429, which showed low level of endogenous osteopontin and paclitaxel sensitive cell line OV420, which showed high level of endogenous osteopontin, and a normal ovarian epithelial (HOSE: Human ovarian surface epithelial) cells were treated with purified osteopontin. Furthermore, OV420 was treated with osteopontin siRNA alone or in combination with paclitaxel. Proliferation rates and cell cycle progression of treated cells were determined by the tetrazolium colorimetric (XTT) assay and FACS analysis, respectively. Results: Exogenous osteopontin increased the proliferation rate of OV429 and OV420 but had negligible effect on normal HOSE. Ovarian cancer cell lines treated with siRNA showed significantly reduced the growth rates (P<0.05), and they were arrested in G2/M phase of the cell cycle. Furthermore, OV420 treated with paclitaxel in the presence of osteopontin siRNA showed significantly decreased the survival rate. Conclusion: Osteopontin promote cell growth in malignant but not in normal ovarian epithelial cells, and may confer paclitaxel-resistance by adhesion to each cell and minimized the cell surface which exposure to chemo-agents.

Osteopontin, Ovarian cancer cell, HOSE, Paclitaxel