• 1.中國醫(yī)學(xué)科學(xué)院中國協(xié)和醫(yī)科大學(xué)北京協(xié)和醫(yī)院普通外科（北京100730）;;
  • 2.中國醫(yī)學(xué)科學(xué)院中國協(xié)和醫(yī)科大學(xué)北京協(xié)和醫(yī)院消化內(nèi)科;;
  • 通迅作者： 陳原稼;

【摘要】目的探討生長抑素類似物（SSTA）能否在體內(nèi)、外抑制結(jié)腸癌細(xì)胞的增殖及其抑制作用的可能機(jī)理。
方法用RT-PCR和原位雜交方法檢測人結(jié)腸癌細(xì)胞株HCT116 生長抑素Ⅱ型受體（SSTR2） mRNA的表達(dá)； 用MTT法檢測奧曲肽(Oct)或SSTR2特異激動劑NC-8-12對胰島素或表皮生長因子刺激下的HCT116細(xì)胞作用24 h后的增殖情況，并用流式細(xì)胞儀檢測其Cyclin D1的表達(dá)； 同時將HCT116細(xì)胞種植于裸鼠皮下，給予其奧曲肽或NC-8-12治療，觀察腫瘤生長情況。
結(jié)果 ①HCT116細(xì)胞株和荷瘤裸鼠癌組織中均有SSTR2 mRNA的表達(dá)； ②胰島素和表皮生長因子能促進(jìn)HCT116細(xì)胞株生長，且這一促進(jìn)作用能部分地被Oct和NC-8-12減弱； ③胰島素刺激下HCT116細(xì)胞的Cyclin D1表達(dá)水平提高，Oct或NC-812作用后其表達(dá)水平下降，但差異無顯著性意義（P gt;0.05）； ④Oct和NC-8-12組裸鼠皮下種植瘤重量和體積與對照組比較差異無顯著性意義（P gt;0.05）。
結(jié)論在體外，Oct及NC-8-12均能抑制HCT116細(xì)胞株增殖，SSTR2參與介導(dǎo)了SSTA抑制結(jié)腸癌細(xì)胞生長的作用； 在本實(shí)驗(yàn)劑量下，Oct和NC-8-12均對接種于裸鼠的人結(jié)腸癌腫瘤生長無影響。

引用本文： 李小毅,陳原稼,唐偉松,李景南,陳元方. 奧曲肽和NC-8-12對人結(jié)腸癌細(xì)胞株HCT116體內(nèi)外生長的影響△. 中國普外基礎(chǔ)與臨床雜志, 2005, 12(1): 23-28. doi: 復(fù)制

1. 陳元方, 張萬岱. 胃腸肽類激素, 生長因子與消化系統(tǒng)非內(nèi)分泌性惡性腫瘤 [A]. 見陳元方主編.胃腸肽類激素基礎(chǔ)與臨床 [M]. 北京: 北京醫(yī)科大學(xué)中國協(xié)和醫(yī)科大學(xué)聯(lián)合出版社, 1997∶752~760.
2. Buscail L, Delesque N, Esteve JP, et al. Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2 [J]. Proc Natl Acad Sci USA, 1994; 91(6)∶2315.
3. Buscail L, Esteve JP, SaintLaurent N, et al. Inhibition of cell proliferation by the somatostatin analogue RC160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms [J]. Proc Natl Acad Sci USA, 1995; 92(5)∶1580.
4. Pages P, Benali N, SaintLaurent N, et al. sst2 somatostatin receptor mediates cell cycle arrest and induction of p27(Kip1). Evidence for the role of SHP1 [J]. J Biol Chem, 1999; 274(21)∶15186.
5. Kubota A, Yamada Y, Kagimoto S, et al. Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201995 in treatment of human endocrine tumors [J]. J Clin Invest, 1994; 93(3)∶1321.
6. Reubi JC, Schaer JC, Waser B, et al. Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization [J]. Cancer Res, 1994; 54(13)∶3455.
7. 李景南，陳元方，錢家鳴，等. 蛙皮素對人胃黏膜上皮永生細(xì)胞系cyclin D1/CDK4 的影響 [J]. 中華內(nèi)科雜志, 2001; 40（6）∶374.
8. Smith JP, Solomon TE. Effects of gastrin, proglumide, and somatostatin on growth of human colon cancer [J]. Gastroenterology, 1988; 95(6)∶1541.
9. Kath R, Hoffken K. The significance of somatostatin analogues in the antiproliferative treatment of carcinomas [J]. Recent Results Cancer Res. 2000;153∶23.
10. Dy DY, Whitehead RH, Morris DL. SMS 201.995 inhibits in vitro and in vivo growth of human colon cancer [J]. Cancer Res, 1992; 52(4)∶917.
11. Qin Y, Schally AV, Willems G. Treatment of liver metastases of human colon cancers in nude mice with somatostatin analogue RC160 [J]. Int J Cancer, 1992; 52(5)∶791.
12. Stewart GJ, Lawson JA, Morris DL. Octreotide inhibits development of hepatic metastases from a human colonic cancer cell line [J]. Br J Surg, 1994; 81(9)∶1332.
13. Arber N, Hibshoosh H, Moss SF, et al. Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis [J]. Gastroenterology, 1996; 110(3)∶669.
14. Salh B, Bergman D, Marotta A, et al. Differential cyclindependent kinase expression and activation in human colon cancer [J]. Anticancer Res, 1999; 19(1B)∶741.
  1. 1. 陳元方, 張萬岱. 胃腸肽類激素, 生長因子與消化系統(tǒng)非內(nèi)分泌性惡性腫瘤 [A]. 見陳元方主編.胃腸肽類激素基礎(chǔ)與臨床 [M]. 北京: 北京醫(yī)科大學(xué)中國協(xié)和醫(yī)科大學(xué)聯(lián)合出版社, 1997∶752~760.
  2. 2. Buscail L, Delesque N, Esteve JP, et al. Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2 [J]. Proc Natl Acad Sci USA, 1994; 91(6)∶2315.
  3. 3. Buscail L, Esteve JP, SaintLaurent N, et al. Inhibition of cell proliferation by the somatostatin analogue RC160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms [J]. Proc Natl Acad Sci USA, 1995; 92(5)∶1580.
  4. 4. Pages P, Benali N, SaintLaurent N, et al. sst2 somatostatin receptor mediates cell cycle arrest and induction of p27(Kip1). Evidence for the role of SHP1 [J]. J Biol Chem, 1999; 274(21)∶15186.
  5. 5. Kubota A, Yamada Y, Kagimoto S, et al. Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201995 in treatment of human endocrine tumors [J]. J Clin Invest, 1994; 93(3)∶1321.
  6. 6. Reubi JC, Schaer JC, Waser B, et al. Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization [J]. Cancer Res, 1994; 54(13)∶3455.
  7. 7. 李景南，陳元方，錢家鳴，等. 蛙皮素對人胃黏膜上皮永生細(xì)胞系cyclin D1/CDK4 的影響 [J]. 中華內(nèi)科雜志, 2001; 40（6）∶374.
  8. 8. Smith JP, Solomon TE. Effects of gastrin, proglumide, and somatostatin on growth of human colon cancer [J]. Gastroenterology, 1988; 95(6)∶1541.
  9. 9. Kath R, Hoffken K. The significance of somatostatin analogues in the antiproliferative treatment of carcinomas [J]. Recent Results Cancer Res. 2000;153∶23.
  10. 10. Dy DY, Whitehead RH, Morris DL. SMS 201.995 inhibits in vitro and in vivo growth of human colon cancer [J]. Cancer Res, 1992; 52(4)∶917.
  11. 11. Qin Y, Schally AV, Willems G. Treatment of liver metastases of human colon cancers in nude mice with somatostatin analogue RC160 [J]. Int J Cancer, 1992; 52(5)∶791.
  12. 12. Stewart GJ, Lawson JA, Morris DL. Octreotide inhibits development of hepatic metastases from a human colonic cancer cell line [J]. Br J Surg, 1994; 81(9)∶1332.
  13. 13. Arber N, Hibshoosh H, Moss SF, et al. Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis [J]. Gastroenterology, 1996; 110(3)∶669.
  14. 14. Salh B, Bergman D, Marotta A, et al. Differential cyclindependent kinase expression and activation in human colon cancer [J]. Anticancer Res, 1999; 19(1B)∶741.