Does HSP27 inhibitory effect of paclitaxel contribute to overcome the drug resistance in gynecologic cancer cells?
| Project/Area Number |
13671758
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | KAWASAKI MEDICAL SCHOOL |
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Principal Investigator |
FUJIWARA Keiichi Kawasaki Medical School Department of Obstetrics and Gynecology, Associate Professor, 医学部, 助教授 (20238629)
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| Co-Investigator(Kenkyū-buntansha) |
KOHNO Ichiro Kawasaki Medical School Department of Obstetrics and Gynecology, Professor, 医学部, 教授 (30108146)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Heat Shock Protein 27 / Cisplatin / Paclitaxel / Drug Resistance / Gvnecologic Cancer Cells / Chemotherapy / HSP27 / 婦人科がん細胞 / 耐性 |
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| Research Abstract |
The aim of this study is to determine if one of the tubulin depolymerization inhibitor, paclitaxel (PTX) contribute to overcome the drug- resistance in gynecologic cancer cells, by focusing the fact that PTX is known to suppress the over expression of heat shock protein 27 (HSP27), which related with the development of drug- resistance
As a preliminary experiment, we tested the correlation between survival and expression of HSP27 in cisplatin sensitive HeLa cells (HS) and resistant variant (HR) using cisplatin and PTX using their 50% inhibitory concentration (IC50) of cell growth. Exposure of single agent cisplatin, paclitaxel, sequential exposure of cisplatin then PTX (CTP), and PTX then cisplatin (PTC) were tested. Cisplatin exposure induced the HSP27 but PTC inhibited the HSP27 expression and cell survival was lowest. However, when we tested this experiment repeatedly, we found that reproducibility was very poor. Therefore, we went back to the basic position to try to find the possible problems such as condition of cell culture and method of experiments. The IC50 was reexamined by dose- response curve and we found that new IC50 of paclitaxel dose not suppress the induction of HSP27. The reasons for this include mutation of the cells, difference of condition in measuring HSP27 and so on. During the extensive experimentation to reveal this problem we found that expression of HSP27 is different between cells floating in the medium and those attached on the flask after paclitaxel or cisplatin exposure. We also found the vast difference between median and mean channel number when measuring HSP27 fluorescent intensity using flow cytometer by the difference of gate setting. We are now currently continuing the experiment to clarify these problems
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Report
(3 results)
Research Products
(9 results)
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[Publications] Kanamori Y, Kigawa J, Itamochi H, Sultana H, Suzuki M, Ohwada M, Kamura T, Sugiyama T, Kikuchi Y, Kita T, Fujiwara K, Terakawa N: "PTEN expression is associated with prognosis for patients with advanced endometrial carcinoma undergoing postoperative chemotherapy"Int J Cancer. 100. 686-689 (2002)
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