Ishizuka J, Townsend C M, Thompson J C
Department of Surgery, University of Texas Medical Branch, Galveston.
Ann Surg. 1993 May;217(5):439-45; discussion 446. doi: 10.1097/00000658-199305010-00003.
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.
NT is trophic for normal rat pancreas, but the effect of NT on growth of human pancreatic cancer is not known.
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.
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.
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.
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。
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。
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。
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。
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。
