Effects of Octreotide and NC-8-12 on the Proliferation of Human Colonic Carcinoma Cell Line HCT116 in vitro and in vivo_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Xiaoyi ¹ , CHEN Yuanjia ² , TANG Weisong ¹ , LI Jingnan ² , CHEN Yuanfang. ²

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730， China;

Corresponding author：

Keywords：

Somatostatin analogue Somatostatin receptor Colonic carcinoma Cyclin D1

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【Abstract】ObjectiveTo investigate the inhibitory effects of somatostatin analogue (SSTA) on the colonic carcinoma cell growth in vitro and in vivo and its possible mechanism.
MethodsThe somatostatin receptor type Ⅱ (SSTR2) mRNA of colonic carcinoma cell line HCT116 was detected by using RTPCR and hybridization in situ. The effects of octreotide (Oct) or NC-8-12 (specific agonist of SSTR2 ) on the proliferation of HCT116 was measured with MTT after HCT116 stimulated by insulin or epidermal growth factor (EGF) and incubated with Oct or NC-8-12 simultaneously for 24 hours. The expression of cyclin D1 was detected with flow cytometry. The HCT116 were implanted in nude mice subcutaneously and treated with Oct or NC-8-12. The tumor volume and tumor weight were measured according to schedule.
Results①SSTR2 mRNA was detected in HCT116 and the tumor implanted in nude mice; ②Insulin and EGF increased the proliferation of HCT116 significantly, and this proliferation could be inhibited by Oct and NC-8-12 partially; ③Insulin increased the Cyclin D1 expression of HCT116, its level decreased slightly when treated with Oct or NC-8-12 but not significantly (P gt;0.05); ④The weight and volume of implanted tumor in nude mice treated with Oct or NC-8-12 showed no significant difference compared with the control group (P gt;0.05).
ConclusionBoth Oct and NC-8-12 could inhibit the proliferation of colonic carcinoma cell line HCT116 in vitro, which indicated that SSTR2 may mediated the inhibition. Oct and NC-8-12 have no effect on the growth of implanted HCT116 in nude mice in this experiment.

Citation： LI Xiaoyi,CHEN Yuanjia,TANG Weisong,LI Jingnan,CHEN Yuanfang.. Effects of Octreotide and NC-8-12 on the Proliferation of Human Colonic Carcinoma Cell Line HCT116 in vitro and in vivo. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2005, 12(1): 23-28. doi: Copy

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7.	李景南，陈元方，钱家鸣，等. 蛙皮素对人胃黏膜上皮永生细胞系cyclin D1/CDK4 的影响 [J]. 中华内科杂志, 2001; 40（6）∶374.
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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. 陈元方, 张万岱. 胃肠肽类激素, 生长因子与消化系统非内分泌性恶性肿瘤 [A]. 见陈元方主编.胃肠肽类激素基础与临床 [M]. 北京: 北京医科大学中国协和医科大学联合出版社, 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，陈元方，钱家鸣，等. 蛙皮素对人胃黏膜上皮永生细胞系cyclin D1/CDK4 的影响 [J]. 中华内科杂志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of Octreotide and NC-8-12 on the Proliferation of Human Colonic Carcinoma Cell Line HCT116 in vitro and in vivo

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