Apoptotic Effect on Pancreatic Adenocarcinoma Cell BxPC-3 in Subcutaneous Transplantation Tumor of Nude Mice Induced by Sulfasalazine and 5-Fluouracil_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUANG Zhe ¹ , GUO Kejian ² , HE Sanguang ²

1. Department of Large Intestinal Surgery of Liaoning Oncology Hospital, Shenyang 110042, China;;
2. Department of General Surgery, The First Affiliated Hospital, China Medical University, Shenyang 110001, ChinaCorresponding Author: HUANG Zhe, E-mail: huangzheming@yahoo.com;

Corresponding author：

Keywords：

Pancreatic adenocarcinoma; 5-Fluouracil; Sulfasalazine; Apoptosis; Nuclear factor-κB; Subcutaneous transplantation tumor

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Objective 　To explore the effect on apoptotic genes of pancreatic adenocarcinoma cell BxPC-3 from subcutaneous transplantation tumor in nude mice induced by 5-FU and sulfasalazine (SZ).
Methods 　Changes of apoptosis-related genes 〔bcl-2, cyclinD1, Bax and NF-κB (p65)〕 in subcutaneous transplantation tumor treated by 5-FU, SZ alone or both at the levels of mRNA and protein were measured by RT-PCR and Western blot.
Results 　NF-κB (p65) at mRNA relative content and protein expression in subcutaneously heterotopic transplantation tumor treated by 5-FU (7.5, 15 mg/kg), SZ (10, 20 mg/kg) alone or both showed significant difference, except for two subsets in SZ group, respectively, in comparison with each control group (P＜0.01). Meanwhile bcl-2 and cyclinD1 at the levels of mRNA and protein, and Bax protein level were significantly different from each control group (P＜0.01). The above-mentioned indexes were show obvious interaction of both by multiple factor analysis of variance.
Conclusion 　Up-regulated level of Bax, down-regulated levels of bcl-2, cyclinD1 and NF-κB (p65) might be one of apoptotic mechanisms that SZ synergistically enhanced apoptotic effect on pancreatic adenocarcinoma cell BxPC-3 of subcutaneous transplantation tumor in nude mice induced by 5-FU.

Citation： HUANG Zhe ,GUO Kejian,HE Sanguang. Apoptotic Effect on Pancreatic Adenocarcinoma Cell BxPC-3 in Subcutaneous Transplantation Tumor of Nude Mice Induced by Sulfasalazine and 5-Fluouracil. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(8): 550-555. doi: Copy

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.	吴晓康，吴育连，郑樟栋，等. 胰腺癌细胞凋亡与bcl-2,bax基因表达 [Ｊ]. 中国普通外科杂志, 2002； 11（3）∶171.
13.	Kumar M , 刘正人, 田锐，等. 生长抑素受体2基因转染抑制胰腺肿瘤细胞生长机制的探讨 [Ｊ]. 中华医学杂志, 2004； 84(9)∶760.
14.	张元，夏曙霞，钱家勤. Bax 基因表达在胰腺癌组织细胞凋亡作用 [Ｊ]. 肝胆外科杂志, 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. 　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. 　吴晓康，吴育连，郑樟栋，等. 胰腺癌细胞凋亡与bcl-2,bax基因表达 [Ｊ]. 中国普通外科杂志, 2002； 11（3）∶171.
13. 　Kumar M , 刘正人, 田锐，等. 生长抑素受体2基因转染抑制胰腺肿瘤细胞生长机制的探讨 [Ｊ]. 中华医学杂志, 2004； 84(9)∶760.
14. 　张元，夏曙霞，钱家勤. Bax 基因表达在胰腺癌组织细胞凋亡作用 [Ｊ]. 肝胆外科杂志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Apoptotic Effect on Pancreatic Adenocarcinoma Cell BxPC-3 in Subcutaneous Transplantation Tumor of Nude Mice Induced by Sulfasalazine and 5-Fluouracil

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