Liebow C, Reilly C, Serrano M, Schally A V
Department of Oral Surgery, State University of New York, Buffalo School of Dental Medicine 14214.
Proc Natl Acad Sci U S A. 1989 Mar;86(6):2003-7. doi: 10.1073/pnas.86.6.2003.
Several analogues of somatostatin were examined in the Mia PaCa-2 human pancreatic cancer cell line for their ability to promote tyrosine phosphatase activity affecting the receptors for the epidermal growth factor. The inhibition of growth of the Mia PaCa-2 cells in culture was also evaluated to determine the mechanism of action of somatostatin analogues and their relative effectiveness in inhibiting cancer growth. Of the analogues tested D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) caused the greatest stimulation of tyrosine phosphatase activity. Analogue D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) had less effect but was more potent than somatostatin-14. Analogue D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol) (SMS 201-995) produced no significant dephosphorylation. The analogues displayed the same order of activity in assays on growth inhibition of Mia PaCa-2 cells in cultures. Analogue (SMS-201-995) caused virtually no tyrosine phosphatase stimulation or growth inhibition in this cancer cell line, although it possesses a much higher antisecretory activity than somatostatin-14 in normal tissues. These observations indicate that somatostatin and some of its analogues can act as growth inhibitors in cancer cells through the activation of tyrosine phosphatase. These data reinforce the view that somatostatin analogue RC-160 and related compounds could be used for treatment of pancreatic cancer.
在Mia PaCa - 2人胰腺癌细胞系中检测了几种生长抑素类似物,以研究它们促进影响表皮生长因子受体的酪氨酸磷酸酶活性的能力。还评估了培养的Mia PaCa - 2细胞生长的抑制情况,以确定生长抑素类似物的作用机制及其在抑制癌症生长方面的相对有效性。在测试的类似物中,D - Phe - Cys - Tyr - D - Trp - Lys - Val - Cys - Trp - NH2(RC - 160)对酪氨酸磷酸酶活性的刺激作用最大。类似物D - Phe - Cys - Tyr - D - Trp - Lys - Val - Cys - Thr - NH2(RC - 121)的作用较小,但比生长抑素 - 14更有效。类似物D - Phe - Cys - Phe - D - Trp - Lys - Thr - Cys - Thr(ol)(SMS 201 - 995)未产生明显的去磷酸化作用。这些类似物在培养的Mia PaCa - 2细胞生长抑制试验中表现出相同的活性顺序。类似物(SMS - 201 - 995)在该癌细胞系中几乎没有引起酪氨酸磷酸酶刺激或生长抑制,尽管它在正常组织中具有比生长抑素 - 14高得多的抗分泌活性。这些观察结果表明,生长抑素及其一些类似物可通过激活酪氨酸磷酸酶在癌细胞中作为生长抑制剂发挥作用。这些数据强化了生长抑素类似物RC - 160及相关化合物可用于治疗胰腺癌的观点。