้บไผๅญๆนๅคใใฆในใขใใซใฎ้็บโใใไบ้ฒใปๆฒป็ใฎใใใฎใใใฏใขใฆใใปใคใใใผใทใงใณ
ใใๅใจๆชๆงๅ้ฒๅฑๆฉๆงใใใในใฑใผใซใงๅฏ่ฆๅใใ
ๅคงๅณถๆญฃไผธใ้ๆฒขๅคงๅญฆใใ็ๅฝ็งๅญฆ็ ็ฉถๆ ๆๆใปไธปไปป็ ็ฉถ่
ๅคงๅณถๆญฃไผธๆๆใฏใใใ็็ฉๅญฆ็ ็ฉถใธใฎ่ฒข็ฎใซใใไธ็็ใซ้ซใ่ฉไพกใใใฆใใใใ็งใฎ็ ็ฉถๅฎคใงใฏใๅคง่ ธใใใใใณ่ใใใฎ็ ็ฉถใ็ฎ็ใจใใฆใ้บไผๅญๆนๅคใใฆในใขใใซใฎ้็บใซๅใ็ตใใงใใพใใใ็งใใกใ้็บใใใขใใซใฏใใใใคใใฎ้่ฆใช็บ่ฆใซใคใชใใฃใฆใใพใใใ
ๅคงๅณถๆๆใฏใ1995ๅนดใซใๅคง่ ธใใใฎๅๅ ใ่งฃๆใใใใใใใฆในใฎ่ๆงๅนน็ดฐ่ใไฝฟใฃใใใใฏใขใฆใใใฆในใไฝ่ฃฝใใ[1]ใ1996ๅนดใซใฏใCOX-2ใ้ปๅฎณใใใใจใง่ ธ็ฎกใใชใผใ็บ็ใๆๅถใใใใใจใใคใพใใCOX-2ใๅคง่ ธใใไบ้ฒใฎใฟใผใฒใใใงใใใใจใใCellใใซ็บ่กจใใ [2]ใใใCellใใง็บ่กจใใใๅคง่ ธใใชใผใใใใณๅคง่ ธใใใฎๆฐใใๅๅญฆไบ้ฒ่ฌ๏ผCOX-2้ปๅฎณ่ฌ๏ผใซ้ขใใๅ ฑๅใฏใ2,000ๅไปฅไธใๅผ็จใใใพใใใใใฎๆๆใฏใใใฎๅพใฎใใๆฒป็ใธใฎๆฐใใ้ใ้ใใพใใใใใพใงใฏใ็ฑณๅฝใงใใๆ็็่ฌใขในใใชใณใใใใไบ้ฒใใใจใใๅ ฑๅใใชใใใฆใใพใใใใใใใใใพใงๆฅใใใจใใๆใใงใใใจใๅคงๅณถๆๆใฏ่ชใใ
ๅณ1 ๅ็ ง1ใฎ็ ็ฉถใงไฝฟใใใใใใฏใขใฆใใใฆใน
่ฟๅนดใๅคงๅณถๆๆใใฏใ่ใใใฎ็บ็ใ็็ใจ้ขไฟใใใใใจใๅ ฑๅใใ็บใใๆงใฎWntใทใฐใใซใจ็็ๆงใฎCOX-2็ต่ทฏใๆดปๆงๅใใใใจใซใใฃใฆใ่ใใใฎ็บ็้็จใใขใใซๅใใGanใใฆในใ้็บใใ [3]ใๅคงๅณถๆๆใซใใใจใใใใใฏใใใฎใใใๅ็พใใๅใฎ่ใใใขใใซใงใใใ
ใใใ็ๅฝ็งๅญฆ็ ็ฉถๆใฎใใญใธใงใฏใใงใฏใใใใๅใใจใๆชๆงๅ้ฒๅฑใใกใซใใบใ ใฎๆฌ่ณชใใใใฌใใซใง็ ็ฉถใใๆฐใใชใใใฎ่จบๆญๆณใจๆฒป็ๆณใ้็บใใใใจ่ใใฆใใพใใ้ซ้ๅๅญ้ๅ้กๅพฎ้ก๏ผ้ซ้AFM๏ผใจ่ตฐๆปๅใคใชใณไผๅฐ้กๅพฎ้ก๏ผSICM๏ผใไฝฟใฃใฆใ่ ซ็็ดฐ่ใฎๅคๅฝขใๆชๆงๅ้ฒๅฑใจใ่ฌ็ฉๅๆ ใฎใใคใใใใฏใชๅคๅใซใใ็ดฐ่ๆง้ ใฎ็ฐๅธธใๅฏ่ฆๅใใใจใจใใซใใใ็ๅฝ็งๅญฆ็ ็ฉถๆใงใใ่จๆธฌๅญฆใฎ็ ็ฉถ่ ใใกใ้็บไธญใฎๆฐใใใใใใญใผใใ็จใใไปฃ่ฌๆธฌๅฎใ่กใใใจ่ใใฆใใพใใใจใๅคงๅณถๆๆใฏ่ชใใ
ๅ ทไฝ็ใซใฏใ็ดฐ่ใฎ่กจ้ขๆง้ ใ็ดฐ่้ชจๆ ผใใใในใฑใผใซใง่ฆณๅฏใใไธ็ฎ้่่ปขๆใฎใใใชๆชๆงๅ้ฒๅฑใฎ้็จใงใใใใใฉใฎใใใซๅคๅใใใใๅฏ่ฆๅใใ่จ็ปใ ใใใใฏใใใ็ดฐ่ใฎ้ฒๅฑใกใซใใบใ ใ็่งฃใใใใใซ้่ฆใชๅฝนๅฒใๆใใใใฎใจๆๅพ ใใใฆใใใ
ๅคงๅณถๆๆใใฏใใใใซๅคง่ ธใใๆชๆงๅใฎไป็ตใฟใ่งฃๆใใใใใๅคง่ ธใใใฎใใพใใพใช้บไผๅญๅค็ฐใจ่กจ็พๅใ่งฃๆใใใๅคงๅณถๆๆใฏใใ็งใใกใไฝ่ฃฝใใA, AK, AKT, AKP, AKTPใชใฉใฎๅคง่ ธใใ็ดฐ่ใณใฌใฏใทใงใณใฏใไปใซ้กใ่ฆใชใใใฎใงใๆช็ขบ่ชใฎๅค็ฐใๅคๆฐๅซใใงใใๅธ่ฒฉใฎใใ็ดฐ่ใจใฏๅคงใใ็ฐใชใใพใใใจๅผท่ชฟใใใ็พๅจใไธ็ฎ้่่ปขๆใจใใๆชๆงๅใฎ็พ่ฑกใฏใ่ตฐๆปๅใ้้ๅ้ปๅญ้กๅพฎ้กใชใฉใซใใ้ๆญข็ปๅใซๅบใฅใใฆ็่งฃใใใฆใใพใใ็งใใกใฏใใใ็ ็ฉถใฎใใใซใชใขใซใฟใคใ ใงๅๆ ใๅฏ่ฆๅใงใใใใใซใใใใจ่ใใฆใใพใใใจๆๆฐ่พผใใใใฎ็ ็ฉถใฏใ้ๆฒขๅคงๅญฆใงใ่ฏๆงใใๆชๆงใพใงใฎใใ็ต็นใใๆจน็ซใใใชใซใฌใใคใ็ดฐ่๏ผA/AK/AKP/AKPT๏ผใ็จใใฆ่กใใใฆใใใ
ใใไธใคใฎ็ ็ฉถใใผใใฏใๅค็ฐๅp53ใฎใใใฉใใผ่คๅๅฝขๆใซ้ขใใใใฎใ ใๅคงๅณถๆๆใใฏๆ่ฟใๅค็ฐๅp53ใฏใใขๆฅๅไฝใงใฏๆ ธใซ่็ฉใใใใ้็ๅp53ใจใฎใใใญๆฅๅใงใฏๆ ธใซ่็ฉใใชใใจใใใใจใ็บ่ฆใใ [Nakayama, et al, Oncogene, 2018]ใๅค็ฐๅp53ใฎๅฑๅจๆงใใฉใฎใใใซๅถๅพกใใใฆใใใใใพใใใฎๅถๅพกใ่คๅไฝๅฝขๆใจ้ขไฟใใใใใซใคใใฆใฏใใใใฎๆชๆงๅใ็่งฃใใใใใซ้่ฆใชๆ ๅ ฑใจใชใใใใพใ ๆใใใซใชใฃใฆใใชใใ
็ ็ฉถใใคใฉใคใ
2018ๅนดใซๅคงๅณถๆๆใใฏๅค้้บไผๅญๅค็ฐใใฆใน๏ผA, K, T, P, Fใฎ็ตใฟๅใใ๏ผใฎไฝ่ฃฝใซ้ขใใ็ ็ฉถๆๆใ็บ่กจใใ้บไผๅญๅค็ฐใจใใใฎ่กจ็พๅใฎ้ขไฟใๆใใใซใใใใใใใฎใใฆในใขใใซใ่ ซ็็ฑๆฅใฎใชใซใฌใใคใใฎ็งปๆคใขใใซใฏใๅคง่ ธใใใฎๆชๆงๅ้ฒๅฑใใญใปในใๅ็พใใฆใใใใใใใฎ็ตๆใฏใ็นๅฎใฎ้บไผๅญๅค็ฐใซไพๅญใใใทใฐใใซ็ต่ทฏใๆจ็ใจใใใใจใงๅคง่ ธใใ่ปข็งปใไบ้ฒใงใใๅฏ่ฝๆงใ็คบใ้่ฆใชๆๆใงใใ[Nakayama, et al, Oncogene, 2017; Sakai, et al, Cancer Res, 2018]ใ
ๅ่ๆ็ฎ
- Oshima et al. โLoss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc geneโ, PNAS, 92, 4482-4486 (1995).
DOI: 10.1073/pnas.92.10.4482 - Oshima et al. โSuppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2)โ, Cell, 87, 803-809, (1996).
- H Oshima et al. โCarcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathwayโ, Gastroenterology, 131, 1086-1095, (2006).
- Sakai, et al. โCombined Mutation of Apc, Kras, and Tgfbr2 Effectively Drives Metastasis of Intestinal Cancerโ, Cancer Res, March 2018.
DOI: 10.1158/0008-5472.CAN-17-3303
ใชใซใฌใใคใใ็จใใ่ ซ็ใฎๅๆง็ฏ
ๅณ2 ๅคง่ ธใใๆชๆงๅ้ฒๅฑใฎ้็จ[ๅ็ ง1]๏ผๅทฆ๏ผใใใณAKTP๏ผ็ท๏ผใจAP๏ผ่ตค๏ผ่ ซ็็ดฐ่ใซใใฃใฆๅๆง็ฏใใใๅคง่ ธใใ็ต็นใฎๅคๆงๆง๏ผๅณ๏ผ
