• 1.東港市中心醫(yī)院普外科(遼寧東港 118300);;
  • 2.中國(guó)醫(yī)科大學(xué)盛京醫(yī)院肝膽乳腺外科(沈陽(yáng) 110004);

目的 探討103鈀(Pd)放射性支架釋放的γ射線對(duì)Fas基因表達(dá)的影響以及與膽管癌細(xì)胞凋亡的關(guān)系及意義
方法 建立人膽管癌裸鼠移植瘤模型； 將建模成功的裸鼠分為實(shí)驗(yàn)組和對(duì)照組，實(shí)驗(yàn)組置入37 MBq 103Pd膽道放射性支架，對(duì)照組置入普通金屬支架； 支架置入后10 d計(jì)算腫瘤體積; 應(yīng)用TUNEL法檢測(cè)膽管癌細(xì)胞凋亡的情況; 免疫組化染色方法檢測(cè)膽管癌細(xì)胞中Fas基因表達(dá)的情況。
結(jié)果 實(shí)驗(yàn)組腫瘤體積較對(duì)照組增長(zhǎng)明顯緩慢(P lt;0.05); 膽管癌細(xì)胞的Fas基因表達(dá)陽(yáng)性率較對(duì)照組明顯增高(P lt;0.05)，且膽管癌細(xì)胞出現(xiàn)明顯凋亡，細(xì)胞凋亡率明顯高于對(duì)照組(P lt;0.01)。
結(jié)論 103Pd放射性支架可誘導(dǎo)人膽管癌裸鼠移植瘤中膽管癌細(xì)胞凋亡，明顯抑制膽管癌細(xì)胞生長(zhǎng)，其可能通過(guò)增強(qiáng)Fas基因表達(dá)促進(jìn)膽管癌細(xì)胞凋亡，可能是103Pd放射性支架治療膽管癌的重要機(jī)理之一，進(jìn)一步為臨床應(yīng)用103Pd放射性支架治療膽管癌提供了理論依據(jù)。

引用本文： 趙曉丹,何貴金. 103鈀放射性支架誘導(dǎo)人膽管癌細(xì)胞凋亡及對(duì)Fas基因表達(dá)的影響. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(3): 224-228. doi: 復(fù)制

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6. Patel T. Cholangiocarcinoma [J]. Nat Clin Pract Gastroenterol Hepatol, 2006; 3(1): 3342.
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10. Uno M, Otsuki T, Yata K, et al. Participation of Fasmediated apoptotic pathway in KB, a human head and neck squamous cell carcinoma cell line, after irradiation [J]. Int J Oncol, 2002; 20(3): 617622.
11. Chakraborty M, Abrams SI, Coleman CN, et al. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccinemediated Tcell killing [J]. Cancer Res, 2004; 64(12): 43284337.
12. Yamamoto T, Yoneda K, Ueta E, et al. Enhanced apoptosis of squamous cell carcinoma cells by interleukin2activated cytotoxic lymphocytes combined with radiation and anticancer drugs [J]. Eur J Cancer, 2000; 36(15): 20072017.
13. Mundle SD, Raza A. Defining the dynamics of selfassembled Fasreceptor activation [J]. Trends Immunol， 2002; 23(4): 187194.
14. Hengartner MO. The biochemistry of apoptosis [J]. Nature, 2000; 407(6805): 770776.
15. Kaufmann SH, Earnshaw WC. Induction of apoptosis by cancer chemotherapy [J]. Exp Cell Res, 2000; 256(1): 4249.
16. Khosravi R, Maya R, Gottlieb T, et al. Rapid ATMdependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage [J]. Proc Natl Acad Sci USA, 1999; 96(26): 1497314977.
17. Schuler M, Green DR. Mechanisms of p53dependent apoptosis [J]. Biochem Soc Trans, 2001; 29(Pt 6): 684688.
18. Sheard MA. Ionizing radiation as a responseenhancing agent for CD95mediated apoptosis [J]. Int J Cancer, 2001; 96(4): 213220.
19. Bratton SB, MacFarlane M, Cain K, et al. Protein complexes activate distinct caspase cascades in death receptor and stressinduced apoptosis [J]. Exp Cell Res, 2000; 256(1): 2733.
  1. 1. Itamochi H, Yamasaki F, Sudo T, et al. Reduction of radiationinduced apoptosis by specific expression of Bcl2 in normal cells [J]. Cancer Gene Ther, 2006; 13(5): 451459.
  2. 2. Peschel RE, Colberg JW, Chen Z, et al. Iodine 125 versus palladium 103 implants for prostate cancer: clinical outcomes and complications [J]. Cancer J, 2004; 10(3): 170174.
  3. 3. Waksman R, Raizner AE, Yeung AC, et al. Use of localised intracoronary beta radiation in treatment of in stent restenosis: the INHIBIT randomised controlled trial [J]. Lancet, 2002; 359(9306): 551557.
  4. 4. 何貴金, 于發(fā)強(qiáng), 高沁怡, 等. 103鈀放射性支架對(duì)Fas基因表達(dá)影響及與膽管癌細(xì)胞凋亡關(guān)系研究 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2007; 14(3): 284286.
  5. 5. He GJ, Sun DD, Ji DW, et al. Induction of biliary cholangiocarcinoma cell apoptosis by 103Pd cholangial radioactive stent γrays [J]. Chin Med J (Engl), 2008; 121(11): 10201024.
  6. 6. Patel T. Cholangiocarcinoma [J]. Nat Clin Pract Gastroenterol Hepatol, 2006; 3(1): 3342.
  7. 7. Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors [J]. Ann Surg, 1996; 224(4): 463473.
  8. 8. Ahrendt SA, Pitt HA. Biliary tract [A]. In: Townsend. Sabiston Textbook of Surgery [M]. 16th ed. Philadelphia: WB Saunders Company, 2003: 10761111.
  9. 9. Catelas I, Petit A, Zukor DJ, et al. Cytotoxic and apoptotic effects of cobalt and chromium ions on J774 macrophages-Implication of caspase3 in the apoptotic pathway [J]. J Mater Sci Mater Med, 2001; 12(1012): 949953.
  10. 10. Uno M, Otsuki T, Yata K, et al. Participation of Fasmediated apoptotic pathway in KB, a human head and neck squamous cell carcinoma cell line, after irradiation [J]. Int J Oncol, 2002; 20(3): 617622.
  11. 11. Chakraborty M, Abrams SI, Coleman CN, et al. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccinemediated Tcell killing [J]. Cancer Res, 2004; 64(12): 43284337.
  12. 12. Yamamoto T, Yoneda K, Ueta E, et al. Enhanced apoptosis of squamous cell carcinoma cells by interleukin2activated cytotoxic lymphocytes combined with radiation and anticancer drugs [J]. Eur J Cancer, 2000; 36(15): 20072017.
  13. 13. Mundle SD, Raza A. Defining the dynamics of selfassembled Fasreceptor activation [J]. Trends Immunol， 2002; 23(4): 187194.
  14. 14. Hengartner MO. The biochemistry of apoptosis [J]. Nature, 2000; 407(6805): 770776.
  15. 15. Kaufmann SH, Earnshaw WC. Induction of apoptosis by cancer chemotherapy [J]. Exp Cell Res, 2000; 256(1): 4249.
  16. 16. Khosravi R, Maya R, Gottlieb T, et al. Rapid ATMdependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage [J]. Proc Natl Acad Sci USA, 1999; 96(26): 1497314977.
  17. 17. Schuler M, Green DR. Mechanisms of p53dependent apoptosis [J]. Biochem Soc Trans, 2001; 29(Pt 6): 684688.
  18. 18. Sheard MA. Ionizing radiation as a responseenhancing agent for CD95mediated apoptosis [J]. Int J Cancer, 2001; 96(4): 213220.
  19. 19. Bratton SB, MacFarlane M, Cain K, et al. Protein complexes activate distinct caspase cascades in death receptor and stressinduced apoptosis [J]. Exp Cell Res, 2000; 256(1): 2733.