• 1. 遼寧省腫瘤醫(yī)院大腸外科（沈陽110042）;;
  • 2.中國醫(yī)科大學(xué)附屬第一醫(yī)院普外科（沈陽110001）;

目的 　探討5-氟尿嘧啶(5-FU)和柳氮磺胺吡啶(sulfasalazine, SZ)對裸鼠皮下移植瘤胰腺癌細胞BxPC-3凋亡基因的作用。
方法 　用RT-PCR和Western blot法分別檢測5-FU及SZ單獨或聯(lián)合作用后裸鼠皮下移植瘤凋亡相關(guān)基因NF-κB (p65)、bcl-2及cyclinD1 mRNA和蛋白表達水平以及Bax蛋白表達水平的變化。
結(jié)果 　5-FU (7.5和15 mg/kg)和SZ(10和20 mg/kg)單獨或聯(lián)合作用裸鼠皮下移植瘤，其NF-κB (p65) mRNA表達相對含量和蛋白表達水平與各自對照組比較，除SZ組2個亞組外，其余各組均明顯降低（P＜0.01）； bcl-2和cyclinD1 在mRNA和蛋白水平以及Bax蛋白表達量與各自對照組比較差異均有統(tǒng)計學(xué)意義（P＜0.01）； 上述指標經(jīng)多因素方差分析顯示二者間有明顯的交互作用。
結(jié)論 　Bax水平上調(diào), bcl-2、cyclinD1及NF-κB (p65)水平下調(diào)可能是SZ可協(xié)同增強5-FU誘導(dǎo)裸鼠皮下移植瘤胰腺癌細胞BxPC-3凋亡的機理之一。

引用本文： 黃喆,郭克建,何三光. 柳氮磺胺吡啶和5-氟尿嘧啶對裸鼠皮下移植瘤胰腺癌細胞BxPC-3凋亡基因的影響. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(8): 550-555. doi: 復(fù)制

1. 　Verma M. Pancreatic cancer epidemiology [Ｊ]. Technol Cancer Res Treat, 2005； 4(3)∶295.
2. 　Saif MW, Sviglin H, Carpenter M. Impact of ethnicity on outcome in pancreatic carcinoma [Ｊ]. JOP, 2005； 6(3)∶246.
3. 　Hahn SA, Bartsch DK. Genetics of hereditary pancreatic carcinoma [Ｊ]. Clin Lab Med, 2005； 25(1)∶117.
4. 　Wang W, Abbruzzese JL, Evans DB, et al. The nuclear factor-κB RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells [Ｊ]. Clin Cancer Res, 1999； 5(1)∶119.
5. 　Wang CY, Mayo MW, Korneluk RG, et al. NF-κB antiapoptotis: induction of TRAF1 and TARF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation [Ｊ]. Science, 1998； 281(5383)∶1680.
6. 　Zong WX, Bash J, Gelinas C. Rel blocks both anti-Fas- and TNF-induced apoptosis and intact Rel transactivation domain is essential for this effect [Ｊ]. Cell Death Differ, 1998；5(11)∶963.
7. 　Jeremias I, Kupatt C, Baumann B, et al. Inhibition of nuclear factor κB activation attenuates apoptosis resistance in lymphoid cells [Ｊ]. Blood, 1998； 91(12)∶4624.
8. 　Wang CY, Cusack JC, Liu R, et al. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB [Ｊ]. Nat Med, 1999； 5(4)∶412.
9. 　Wolff R A, Chiao P, Lenzi R, et al. Current approaches and future strategies for pancreatic carcinoma [Ｊ]. Investigational New Drugs, 2000； 18(1)∶43.
10. 　Sharma J, Srinivasan R, Majumdar S, et al. BCL-XL protein levels determine apoptotic index in pancreatic carcinoma [Ｊ]. Pancreas, 2005； 30(4)∶337.
11. 　Brazdil J, Lukas Z, Hermanova M, et al. Apoptosis and expression of bcl-2 protein in invasive ductal adenocarcinoma of the pancreas [Ｊ]. Cesk Patol， 2003; 39(4)∶168.
12. 　吳曉康， 吳育連， 鄭樟棟， 等. 胰腺癌細胞凋亡與bcl-2,bax基因表達 [Ｊ]. 中國普通外科雜志, 2002； 11（3）∶171.
13. 　Kumar M , 劉正人, 田銳， 等. 生長抑素受體2基因轉(zhuǎn)染抑制胰腺腫瘤細胞生長機制的探討 [Ｊ]. 中華醫(yī)學(xué)雜志, 2004； 84(9)∶760.
14. 　張元， 夏曙霞， 錢家勤. Bax 基因表達在胰腺癌組織細胞凋亡作用 [Ｊ]. 肝膽外科雜志, 2002； 10（5）∶344.
15. 　Yip-Schneider MT, Nakshatri H, Sweeney CJ, et al. Parthenolide and sulindac cooperate to mediate growth suppression and inhibit the nuclear factor-kappa B pathway in pancreatic carcinoma cells [Ｊ]. Mol Cancer Ther, 2005； 4(4)∶587.
16. 　Muerkoster S, Arlt A, Sipos B, et al. Increased expression of the E3-ubiquitin ligase receptor subunit beta TRCP1 relates to constitutive nuclear factor-kappaB activation and chemoresistance in pancreatic carcinoma cells [Ｊ]. Cancer Res, 2005； 65(4)∶1316.
17. 　Muerkoster S, Arlt A, Witt M, et al. Usage of the NF-kappaB inhibitor sulfasalazine as sensitizing agent in combined chemotherapy of pancreatic cancer [Ｊ]. Int J Cancer， 2003； 104(4)∶469.
18. 　Fahy BN, Schlieman M, Virudachalam S, et al. AKT inhibition is associated with chemosensitisation in the pancreatic cancer cell line MIA-PaCa-2 [Ｊ]. Br J Cancer, 2003； 89(2)∶391.
19. 　Saleem M, Kaur S, Kweon MH, et al. Lupeol, a fruit and vegetable based triterpene, induces apoptotic death of human pancreatic adenocarcinoma cells via inhibition of Ras signaling pathway [Ｊ]. Carcinogenesis, 2005； 26(11)∶1956.
20. 　Schneider G, Weber A, Zechner U, et al. GADD45alpha is highly expressed in pancreatic ductal adenocarcinoma cells and required for tumor cell viability [Ｊ]. Int J Cancer, 2006； 118(10)∶2405.
21. 　Trauzold A， Schmiedel S, Roder C, et al. Multiple and synergistic deregulations of apoptosis controling genes in pancreatic carcinoma cells [Ｊ]. Br J Cancer, 2003； 89(2)∶1714.
22. 　Mouria M, Gukovskaya AS, Jung Y, et al. Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis [Ｊ]. Int J Cancer, 2002； 98(5)∶761.
  1. 1. 　Verma M. Pancreatic cancer epidemiology [Ｊ]. Technol Cancer Res Treat, 2005； 4(3)∶295.
  2. 2. 　Saif MW, Sviglin H, Carpenter M. Impact of ethnicity on outcome in pancreatic carcinoma [Ｊ]. JOP, 2005； 6(3)∶246.
  3. 3. 　Hahn SA, Bartsch DK. Genetics of hereditary pancreatic carcinoma [Ｊ]. Clin Lab Med, 2005； 25(1)∶117.
  4. 4. 　Wang W, Abbruzzese JL, Evans DB, et al. The nuclear factor-κB RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells [Ｊ]. Clin Cancer Res, 1999； 5(1)∶119.
  5. 5. 　Wang CY, Mayo MW, Korneluk RG, et al. NF-κB antiapoptotis: induction of TRAF1 and TARF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation [Ｊ]. Science, 1998； 281(5383)∶1680.
  6. 6. 　Zong WX, Bash J, Gelinas C. Rel blocks both anti-Fas- and TNF-induced apoptosis and intact Rel transactivation domain is essential for this effect [Ｊ]. Cell Death Differ, 1998；5(11)∶963.
  7. 7. 　Jeremias I, Kupatt C, Baumann B, et al. Inhibition of nuclear factor κB activation attenuates apoptosis resistance in lymphoid cells [Ｊ]. Blood, 1998； 91(12)∶4624.
  8. 8. 　Wang CY, Cusack JC, Liu R, et al. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB [Ｊ]. Nat Med, 1999； 5(4)∶412.
  9. 9. 　Wolff R A, Chiao P, Lenzi R, et al. Current approaches and future strategies for pancreatic carcinoma [Ｊ]. Investigational New Drugs, 2000； 18(1)∶43.
  10. 10. 　Sharma J, Srinivasan R, Majumdar S, et al. BCL-XL protein levels determine apoptotic index in pancreatic carcinoma [Ｊ]. Pancreas, 2005； 30(4)∶337.
  11. 11. 　Brazdil J, Lukas Z, Hermanova M, et al. Apoptosis and expression of bcl-2 protein in invasive ductal adenocarcinoma of the pancreas [Ｊ]. Cesk Patol， 2003; 39(4)∶168.
  12. 12. 　吳曉康， 吳育連， 鄭樟棟， 等. 胰腺癌細胞凋亡與bcl-2,bax基因表達 [Ｊ]. 中國普通外科雜志, 2002； 11（3）∶171.
  13. 13. 　Kumar M , 劉正人, 田銳， 等. 生長抑素受體2基因轉(zhuǎn)染抑制胰腺腫瘤細胞生長機制的探討 [Ｊ]. 中華醫(yī)學(xué)雜志, 2004； 84(9)∶760.
  14. 14. 　張元， 夏曙霞， 錢家勤. Bax 基因表達在胰腺癌組織細胞凋亡作用 [Ｊ]. 肝膽外科雜志, 2002； 10（5）∶344.
  15. 15. 　Yip-Schneider MT, Nakshatri H, Sweeney CJ, et al. Parthenolide and sulindac cooperate to mediate growth suppression and inhibit the nuclear factor-kappa B pathway in pancreatic carcinoma cells [Ｊ]. Mol Cancer Ther, 2005； 4(4)∶587.
  16. 16. 　Muerkoster S, Arlt A, Sipos B, et al. Increased expression of the E3-ubiquitin ligase receptor subunit beta TRCP1 relates to constitutive nuclear factor-kappaB activation and chemoresistance in pancreatic carcinoma cells [Ｊ]. Cancer Res, 2005； 65(4)∶1316.
  17. 17. 　Muerkoster S, Arlt A, Witt M, et al. Usage of the NF-kappaB inhibitor sulfasalazine as sensitizing agent in combined chemotherapy of pancreatic cancer [Ｊ]. Int J Cancer， 2003； 104(4)∶469.
  18. 18. 　Fahy BN, Schlieman M, Virudachalam S, et al. AKT inhibition is associated with chemosensitisation in the pancreatic cancer cell line MIA-PaCa-2 [Ｊ]. Br J Cancer, 2003； 89(2)∶391.
  19. 19. 　Saleem M, Kaur S, Kweon MH, et al. Lupeol, a fruit and vegetable based triterpene, induces apoptotic death of human pancreatic adenocarcinoma cells via inhibition of Ras signaling pathway [Ｊ]. Carcinogenesis, 2005； 26(11)∶1956.
  20. 20. 　Schneider G, Weber A, Zechner U, et al. GADD45alpha is highly expressed in pancreatic ductal adenocarcinoma cells and required for tumor cell viability [Ｊ]. Int J Cancer, 2006； 118(10)∶2405.
  21. 21. 　Trauzold A， Schmiedel S, Roder C, et al. Multiple and synergistic deregulations of apoptosis controling genes in pancreatic carcinoma cells [Ｊ]. Br J Cancer, 2003； 89(2)∶1714.
  22. 22. 　Mouria M, Gukovskaya AS, Jung Y, et al. Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis [Ｊ]. Int J Cancer, 2002； 98(5)∶761.