་ ඹ ᵝ ᘧ 㸯
Ꮫ ㄳ ồ ㄽ ᩥ ࡢ ෆ ᐜ ࡢ せ ᪨
ㄽ ᩥ ᥦ ฟ ⪅ Ặ ྡ ⭘ ⒆ ไ ᚚ ⛉ Ꮫ 㡿 ᇦ ፬ ே ⛉ ⭘ ⒆ Ꮫ ᩍ ⫱ ◊ ✲ ศ 㔝
Ặ ྡ ᑠ ᒣ ᩥ ᮃ ᜨ 㸦 ㄽ ᩥ 㢟 ┠ 㸧
Morphological analysis of peritoneal dissemination of ovarian cancer based on levels of carbonyl reductase 1 expression
㸦Carbonyl reductase 1 Ⓨ ⌧ ⛬ ᗘ ࡼ ࡿ ༸ ᕢ ⒴ ⭡ ⭷ ✀ ࡢ ᙧ ែ Ꮫ ⓗ ゎ ᯒ 㸧
㸦 ෆ ᐜ ࡢ せ ᪨ 㸸 㸧
࠙ ⥴ ゝ ࠚ
Carbonyl reductase 1(CR1)ࡣ NADPH ౫ Ꮡ ᛶ ࡢ ࢝ ࣝ ࣎ ࢽ ࣝ 㑏 ඖ 㓝 ⣲ ࡢ ୍ ࡘ ࡛ 㸪in vivo ࡛ ࡢ ඛ ⾜ ◊ ✲ ࡛ ࡣ ࣄ ࢺ ༸ ᕢ ⒴ ⣽ ⬊ CR1 ࢆ ᙉ Ⓨ ⌧ ࡉ ࡏ ࡿ ⭘ ⒆ ቑ Ṫ ࡀ ᢚ ไ ࡉ
ࢀ 㸪Ⓨ ⌧ ࢆ ప ୗ ࡉ ࡏ ࡿ ⭘ ⒆ ቑ Ṫ ཬ ࡧ ᾐ ₶ ㌿ ⛣ ࡀ ஹ 㐍 ࡍ ࡿ ሗ ࿌ ࡉ ࢀ ࡚ ࠸ ࡿ 㸬ࡲ ࡓ 㸪 ᢠ ⭘ ⒆ ຠ ᯝ ࡢ ᶵ ᗎ ࡋ ࡚ CR1 ࡀ ࣏ ࢺ ࣮ ࢩ ࢫ ࢆ ㄏ ᑟ ࡍ ࡿ ሗ ࿌ ࡉ ࢀ ࡚ ࠸ ࡿ 㸬
ࡑ ࡇ ࡛ ᮏ ◊ ✲ ࡛ ࡣ 㸪ே ᕤ ࣄ ࢺ ⭡ ⭷ ⤌ ⧊ ࢆ ⏝ ࠸ ࡚ CR1 ࡢ Ⓨ ⌧ ⛬ ᗘ ࡼ ࡗ ࡚ ࣄ ࢺ ༸ ᕢ
⒴ ⣽ ⬊ ࡢ ື ែ ࡀ ࡢ ࡼ ࠺ ኚ ࡍ ࡿ ࡢ ᳨ ウ ࡍ ࡿ ࡇ ࢆ ┠ ⓗ ࡋ ࡓ 㸬
࠙ ᪉ ἲ ࠚ
ࣜ ࣏ ࣇ ࢙ ࢡ ࢱ ࣑ ࣥ ἲ ࡚ CR1-DNAࢆ ᑟ ධ ࡋ ࡚ ᙉ Ⓨ ⌧ ࡉ ࡏ ࡓ HRA⣽ ⬊㸦 ࣄ ࢺ ₢ ᾮ ᛶ ༸ ᕢ ⒴ ⣽ ⬊ 㸧㸪CR1-siRNA ᑟ ධ ࡼ ࡗ ࡚ Ⓨ ⌧ ࢆ ప ୗ ࡉ ࡏ ࡓ HRA ⣽ ⬊ 㸪㑇 ఏ Ꮚ ᑟ ධ
ࢆ ⾜ ࢃ ࡞ ࡗ ࡓ HRA ⣽ ⬊㸦 ࢥ ࣥ ࢺ ࣟ ࣮ ࣝ 㸧ࡢ 3 ✀ 㢮 ࢆ ே ᕤ ࣄ ࢺ ⭡ ⭷ ⤌ ⧊ ✀ ࡉ ࡏ 㸪
⒴ ᛶ ⭡ ⭷ ⅖ ᙧ ᡂ ࡲ ࡛ ࡢ 㐣 ⛬ ࢆ 6㸪24㸪48㸪72 㛫 ᚋ ⤒ ⓗ ほ ᐹ ࡋ ࡓ 㸬ࡲ ࡓ TUNEL ἲ 㸪 㟁 Ꮚ 㢧 ᚤ 㙾 ࢆ ⏝ ࠸ 㸪 ࢥ ࣥ ࢺ ࣟ ࣮ ࣝ ⩌ 㸪CR1-DNA ᑟ ධ ⩌ 㸪CR1-siRNA ⩌ ࡢ ே ᕤ
⭡ ⭷ ⤌ ⧊ ୖ ࡢ ࣏ ࢺ ࣮ ࢩ ࢫ ⣽ ⬊ ࢆ ẚ ㍑ ࡋ ࡓ 㸬
ࡲ ࡓ ᇵ 㣴 ⣽ ⬊ ࢆ ⏝ ࠸ ࡚ 㸪1) ࣇ ࣟ ࣮ ࢧ ࢺ ࣓ ࢺ ࣜ ࣮ ࡛ ࣏ ࢺ ࣮ ࢩ ࢫ ⣽ ⬊ ࡢ ྜ 㸪2) Ki-67 㝧 ᛶ ⣽ ⬊ ᩘ 㸪3) ࢘ ࢚ ࢫ ࢱ ࣥ ࣈ ࣟ ࢵ ࢺ ἲ ࡛ caspase-3 ࡢ Ⓨ ⌧ ᙉ ᗘ ࢆ ẚ ㍑ ࡋ ࡓ 㸬
࠙ ⤖ ᯝ ࠚ
6 㛫 ᚋ ࡛ ࡣ 㸪 ࢥ ࣥ ࢺ ࣟ ࣮ ࣝ ⩌ 㸪CR1-DNA ᑟ ධ ⩌ 㸪CR1-siRNA ⩌ ࠸ ࡎ ࢀ ࡶ ⒴ ⣽
⬊ ࡢ ୰ ⓶ ࡢ ᥋ ╔ ࡣ ᕪ ࢆ ㄆ ࡵ ࡞ ࡗ ࡓ 㸬24 㛫 ௨ 㝆 ࡛ ࡣ ୰ ⓶ ୗ ධ ࡋ ࡓ ᚋ ࡢ ⣽
⬊ ቑ Ṫ ࡀ 㸪CR1-DNA ᑟ ධ ⩌ ࡛ ࡣ ࡢ 2 ⩌ ẚ ࡚ ᭷ ព ᢚ ไ ࡉ ࢀ ࡚ ࠸ ࡓ 㸬48 㛫 ᚋ ࡛ ࡣ 㸪CR1-siRNA ⩌ ࡛ ⣽ ⬊ ቑ Ṫ ࡀ ᭷ ព ஹ 㐍 ࡋ ࡚ ࠾ ࡾ 㸪72 㛫 ᚋ ࡛ ࡣ CR1-siRNA
⩌ ࡛ ⒴ ⣽ ⬊ ࡢ 㛫 ㉁ ࡢ ᾐ ₶ ࢆ ㄆ ࡵ ࡓ 㸬
TUNEL ἲ ࡛ ࡣ 㸪CR1-DNAᑟ ධ ⩌ ࡛ ᭷ ព ࡞ ࣏ ࢺ ࣮ ࢩ ࢫ ⣽ ⬊ ࡢ ቑ ຍ ࢆ ㄆ ࡵ 㸪㟁 Ꮚ 㢧 ᚤ 㙾 ࡛ ࣏ ࢺ ࣮ ࢩ ࢫ ᑠ య ࡀ ☜ ㄆ ࡉ ࢀ ࡓ 㸬 ᇵ 㣴 ⣽ ⬊ ࢆ ⏝ ࠸ ࡓ ࣇ ࣟ ࣮ ࢧ ࢺ ࣓ ࢺ ࣜ ࣮
࡛ ࡣ 㸪CR1-DNA ᑟ ධ ⩌ ࡛ ࣏ ࢺ ࣮ ࢩ ࢫ ⣽ ⬊ ࡢ ᭷ ព ࡞ ቑ ຍ ࡀ ☜ ㄆ ࡉ ࢀ ࡓ 㸬 ࡲ ࡓ 㸪 CR1-siRNA ⩌ ࡛ ࡣ Ki-67 㝧 ᛶ ⣽ ⬊ ࡀ ᭷ ព Ⓨ ⌧ ࡋ ࡚ ࠸ ࡓ 㸬caspase-3 ࡣ CR1-DNA ᑟ ධ ⩌ ࡛ Ⓨ ⌧ ࡀ ቑ ຍ ࡋ CR1-siRNA ⩌ ࡛ ࡣ Ⓨ ⌧ ࡀ ప ୗ ࡋ ࡚ ࠸ ࡓ 㸬
࠙ ⪃ ᐹ ࠚ
CR1 ࢆ ᙉ Ⓨ ⌧ 㸪 Ⓨ ⌧ ప ୗ ࡉ ࡏ ࡚ ࡶ ༸ ᕢ ⒴ ⣽ ⬊ ࡣ ࠸ ࡎ ࢀ ࡶ ୰ ⓶ ࡢ ᥋ ╔ ࡣ ᙳ 㡪 ࡋ
࡞ ࡗ ࡓ ࡀ 㸪CR1 Ⓨ ⌧ ࡢ ⛬ ᗘ ࡣ ୰ ⓶ ୗ ࡛ ࡢ ቑ Ṫ 㸪 ᾐ ₶ స ⏝ ࡋ ࡚ ࠸ ࡓ 㸬 ࡍ ࡞ ࢃ ࡕ ࠊ CR1 ࢆ ᙉ Ⓨ ⌧ ࡉ ࡏ ࡿ ⣽ ⬊ ቑ Ṫ ࡣ ᢚ ไ ࡉ ࢀ 㸪CR1 ࢆ Ⓨ ⌧ ప ୗ ࡉ ࡏ ࡿ ⣽ ⬊ ቑ Ṫ ࡣ ஹ
㐍 ࡉ ࢀ 㛫 ㉁ ࡢ ᾐ ₶ ࡶ ㄆ ࡵ ࡓ 㸬ࡇ ࢀ ࡣ 㸪ඛ ⾜ ◊ ✲ ࡢ ࣐ ࢘ ࢫ in vivo ࡢ ᐇ 㦂 ྠ ᵝ ࡢ ⤖ ᯝ ࡛ ࠶ ࡗ ࡓ 㸬 ࡲ ࡓ 㸪TUNEL ἲ 㸪 㟁 Ꮚ 㢧 ᚤ 㙾 ࡢ ⤖ ᯝ ࡽ CR1 ࡢ ⭘ ⒆ ᢚ ไ ຠ ᯝ ࡣ
࣏ ࢺ ࣮ ࢩ ࢫ ࡀ 㛵 ࡋ ࡚ ࠸ ࡿ ࡇ ࡀ ᅇ ࡢ ⤖ ᯝ ࡽ ♧ ၀ ࡉ ࢀ ࡓ 㸬ࡲ ࡓ CR1 Ⓨ ⌧ ప ୗ ⩌
࡛ ࡣ 㸪Ki-67㝧 ᛶ ⣽ ⬊ ࡀ ቑ ຍ ࡋ ࡚ ࠸ ࡓ ࡇ ࡼ ࡾ ⭘ ⒆ ቑ Ṫ ⬟ ࡢ ஹ 㐍 ࡶ ⋓ ᚓ ࡋ ࡚ ࠸ ࡿ ⪃
࠼ ࡽ ࢀ ࡓ 㸬
࠙ ⤖ ㄽ ࠚ
in vivo ࡛ ド ᫂ ࡉ ࢀ ࡚ ࠸ ࡓ CR1 ࡢ Ⓨ ⌧ ⛬ ᗘ ࡼ ࡿ ⭘ ⒆ ቑ Ṫ ࡢ ᕪ ࢆ 㸪in vitro ⤌ ⧊ ࣔ ࢹ ࣝ ࡛ ࠶ ࡿ ே ᕤ ࣄ ࢺ ⭡ ⭷ ⤌ ⧊ ࡛ ࡶ ྠ ᵝ ࡢ ⤖ ᯝ ࢆ ᚓ ࡿ ࡇ ࡀ ࡛ ࡁ ࡓ 㸬CR1 ࡣ ᪂ ࡓ ࡞ ༸ ᕢ ⒴ ⒪ ᡓ ␎ ࡢ ᶆ ⓗ ศ Ꮚ ࡞ ࡾ ᚓ ࡿ ࡇ ࡀ ♧ ၀ ࡉ ࢀ ࡓ 㸬
ͤ1 எ ࡢ ሙ ྜ 㸪ۑ ۑ 㡿 ᇦ ۑ ۑ ᩍ ⫱ ◊ ✲ ศ 㔝 ࠼ ࡚ 㸪ᡤ ᒓ ࡢ ۑ ۑ ㅮ ᗙ ࢆ グ ධ ࡍ ࡿ ࡇ ࠋ
ͤ2 ㄽ ᩥ 㢟 ┠ ࡀ ⱥ ᩥ ࡢ ሙ ྜ ࡣ 㸦 㸧 ෆ ヂ ࢆ グ ࡍ ࡿ ࡇ ࠋ
