SOMATOSTATIN ANALOGS INHIBIT GROWTH OF PANCREATIC-CANCER BY STIMULATING TYROSINE PHOSPHATASE
SOMATOSTATIN ANALOGS INHIBIT GROWTH OF PANCREATIC-CANCER BY STIMULATING TYROSINE PHOSPHATASE
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DOI：
10.1073/pnas.86.6.2003
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发表时间：
1989-03-01
影响因子：
11.1
通讯作者：
SCHALLY, AV
中科院分区：
文献类型：
--
作者：
LIEBOW, C;REILLY, C;SCHALLY, AV
在Mia PaCa-2人胰腺癌细胞系中，研究了几种生长抑素类似物促进酪氨酸磷酸酶活性的能力，这些酶影响表皮生长因子的受体。我们还评估了生长抑素类似物对培养的Mia PaCa-2细胞生长的抑制作用，以确定生长抑素类似物的作用机制及其抑制肿瘤生长的相对有效性。在测试的类似物中，d - ph - cys - tyr - d - trp - lys - val - cys - trp - nh2 （RC-160）对酪氨酸磷酸酶活性的刺激最大。类似物d - ph - 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 - trys - thr - cys - thr (ol) （SMS 201-995）没有产生显著的去磷酸化。这些类似物在培养的Mia PaCa-2细胞生长抑制试验中显示出相同的活性顺序。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，生长抑素及其类似物可以通过激活酪氨酸磷酸酶在癌细胞中发挥生长抑制剂的作用。这些数据加强了生长抑素类似物RC-160及相关化合物可用于治疗胰腺癌的观点。
Serval 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 growth of the Mia PaCa-2 cells in cultrure 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 tissue. 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 compound could be used for treatment of pancreatic cancer.