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[奥曲肽对肝癌细胞体外及体内生长的抑制作用]

[Inhibition effects of octreotide on the growth of hepatocellular carcinoma in vitro and in vivo].

作者信息

Wang C, Tang C, Tang L

机构信息

Department of Gastroenterology, First Hospital, Chongqing University of Medical Sciences, Chongqing, 400016 China.

出版信息

Zhonghua Yi Xue Za Zhi. 2001 Oct;81(19):1194-7.

Abstract

OBJECTIVE

To investigate the effects of somatostatin analogue octreotide on the proliferation and apoptosis of human hepatocellular carcinoma (HCC) cell line as well as the growth of HCC xenografts in nude mice.

METHODS

The effects of octreotide on the proliferation and apoptosis of SMMC-7721 HCC cells was measured by 3H-thymidine incorporation into DNA and the TdT-mediated dUTP nick end labeling assay (TUNEL) or flow cytometric assay separately. Nude mice bearing xenografts of the cell line were treated with octreotide or saline as a control daily until eight weeks after tumor implantation.

RESULTS

Incubation with octreotide decreased 3H-thymidine incorporation into DNA of SMMC-7721 cells by approximately 50% at a concentration of 1 mumol/L. The inhibit effect of octreotide showed a concentration dependence. After 96 h incubation, total cell count was decreased 52.2% compared with control. When cells were treated by octreotide at 1 x 10(-6) mol/L for 24 hours, the apoptosis rates was (15.2 +/- 2.4)%. At necropsy, in mice given octreotide, the mean tumor weight were significantly lower than that of control group (0.27 +/- 0.05 vs 0.85 +/- 0.37, P < 0.01). The inhibition rate of tumor in vivo at 2 months was 68.2%.

CONCLUSION

Octreotide is effective in inhibiting growth of HCC both in vivo and in vitro significantly. The mechanisms of antineoplastic effect action may involved in inhibiting DNA synthesize and inducing apoptosis of tumor cells.

摘要

目的

研究生长抑素类似物奥曲肽对人肝癌细胞系增殖、凋亡的影响以及对裸鼠肝癌移植瘤生长的作用。

方法

分别采用3H-胸腺嘧啶核苷掺入DNA法、TdT介导的dUTP缺口末端标记法(TUNEL)或流式细胞术检测奥曲肽对SMMC-7721肝癌细胞增殖和凋亡的影响。将荷该细胞系移植瘤的裸鼠每日用奥曲肽或生理盐水作为对照进行处理,直至肿瘤接种后8周。

结果

在浓度为1μmol/L时,奥曲肽孵育可使SMMC-7721细胞的3H-胸腺嘧啶核苷掺入DNA量减少约50%。奥曲肽的抑制作用呈浓度依赖性。孵育96小时后,细胞总数与对照组相比减少了52.2%。当细胞用1×10(-6)mol/L奥曲肽处理24小时时,凋亡率为(15.2±2.4)%。尸检时,给予奥曲肽的小鼠平均肿瘤重量明显低于对照组(0.27±0.05 vs 0.85±0.37,P<0.01)。2个月时体内肿瘤抑制率为68.2%。

结论

奥曲肽在体内外均能显著抑制肝癌生长。其抗肿瘤作用机制可能与抑制DNA合成和诱导肿瘤细胞凋亡有关。

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