神经降压素调节人类胰腺癌的生长。
Neurotensin regulates growth of human pancreatic cancer.
作者信息
Ishizuka J, Townsend C M, Thompson J C
机构信息
Department of Surgery, University of Texas Medical Branch, Galveston.
出版信息
Ann Surg. 1993 May;217(5):439-45; discussion 446. doi: 10.1097/00000658-199305010-00003.
OBJECTIVE
The effect of neurotensin (NT) on in vitro-growth of human pancreatic cancer cells (MIA PaCa-2) was examined. Furthermore, the intracellular signal-transduction pathways by which neurotensin regulates growth of MIA PaCa-2 cells were determined.
SUMMARY BACKGROUND DATA
NT is trophic for normal rat pancreas, but the effect of NT on growth of human pancreatic cancer is not known.
METHODS
Effects of NT (10(-12) to 10(-6) mol/l) on growth of MIA PaCa-2 cells were determined by both count of cell numbers and 3H-thymidine incorporation. Action of NT on phosphatidylinositol (PI) hydrolysis, cyclic AMP production, and intracellular calcium level were determined by conventional methods. The effects of 8-bromo-cyclic AMP and prostaglandin E2 on cell growth were determined.
RESULTS
Low concentrations of NT (10(-12) to 10(-9) mol/l) stimulated growth in a dose-dependent manner, but higher concentrations of NT (10(-8) to 10(-6) mol/l) did not stimulate growth of MIA PaCa-2 cells. NT (10(-12) to 10(-6) mol/l) stimulated PI hydrolysis and increased intracellular calcium levels in a dose-dependent manner. High concentrations of NT (10(-8) to 10(-6) mol/l) stimulated production of cyclic AMP in a dose-dependent manner. 8-bromo-cyclic AMP inhibited growth of MIA PaCa-2 cells; prostaglandin E2 did not affect growth of MIA PaCa-2 cells.
CONCLUSIONS
NT stimulates growth of MIA PaCa-2 cells through stimulation of PI hydrolysis and mobilization of calcium. Stimulation of the cyclic AMP pathway by high concentrations of NT abolishes the growth-stimulatory effect of NT that is mediated through PI hydrolysis or calcium mobilization.
目的
研究神经降压素（NT）对人胰腺癌细胞（MIA PaCa-2）体外生长的影响。此外，还确定了神经降压素调节MIA PaCa-2细胞生长的细胞内信号转导途径。
总结背景数据
NT对正常大鼠胰腺具有营养作用，但NT对人胰腺癌生长的影响尚不清楚。
方法
通过细胞计数和3H-胸腺嘧啶核苷掺入法测定NT（10^(-12)至10^(-6)mol/L）对MIA PaCa-2细胞生长的影响。采用常规方法测定NT对磷脂酰肌醇（PI）水解、环磷酸腺苷生成和细胞内钙水平的作用。测定8-溴环磷酸腺苷和前列腺素E2对细胞生长的影响。
结果
低浓度的NT（10^(-12)至10^(-9)mol/L）以剂量依赖方式刺激生长，但高浓度的NT（10^(-8)至10^(-6)mol/L）不刺激MIA PaCa-2细胞生长。NT（10^(-12)至10^(-6)mol/L）以剂量依赖方式刺激PI水解并增加细胞内钙水平。高浓度的NT（10^(-8)至10^(-6)mol/L）以剂量依赖方式刺激环磷酸腺苷生成。8-溴环磷酸腺苷抑制MIA PaCa-2细胞生长；前列腺素E2不影响MIA PaCa-2细胞生长。
结论
NT通过刺激PI水解和钙动员来刺激MIA PaCa-2细胞生长。高浓度NT对环磷酸腺苷途径的刺激消除了通过PI水解或钙动员介导的NT的生长刺激作用。
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