Medullary thyroid carcinoma (MTC) is a rare neuroendocrine neoplasm of the parafollicular thyroid C cells. Although somatostatin receptors are expressed by MTCs, treatment with octreotide has shown poor efficacy, whereas recently pasireotide has demonstrated antiproliferative effects in persistent postoperative MTCs.

Aim of this study was to test the effects of octreotide and pasireotide on MTC cells proliferation, cell cycle proteins expression, MAPK activation, apoptosis, calcitonin secretion, migration and invasion in TT cell line as well as in primary MTC cultured cells. Our results showed that both octreotide and pasireotide reduced TT cell proliferation (-35.2±12.1%, p<0.001, and -25.3±24.8%, p<0.05, at 10^-8 M, respectively), with concomitant inhibition of ERK phosphorylation and cyclin D1 expression. This cytostatic effect was accompanied by a proapoptotic action, with an increase of caspase3/7 activity of 1.5-fold. Moreover, both octreotide and pasireotide inhibited cell migration (-50.9±11.3%, p<0.01, and -40.5±17%, p<0.05, respectively) and invasion (-61.3±35.1%, p<0.05, and -49.7±18%, p<0.01, respectively). No effect was observed on calcitonin secretion. We then tried to extend these observations to primary cultures (n=5). Octreotide and/or pasireotide were effective in reducing cells proliferation in 3 out of 5 tumors, and to induce cell apoptosis in 1 out of 3 MTCs. Both octreotide and pasireotide were able to reduce cell migration in all MTC tested. SST2, SST3 and SST5 were expressed in all MTC, with a tendency to increased expression of SST2 in RET mutated vs wild type MTCs. In agreement, inhibition of mutated RET in TT cells reduced SST2 expression.

In conclusion, we demonstrated that octreotide and pasireotide inhibited cell proliferation and invasiveness in a subset of MTC, supporting their potential use in the control of tumor growth.

甲状腺髓样癌 (MTC) 是一种罕见的甲状腺滤泡旁 C 细胞神经内分泌肿瘤。尽管生长抑素受体由 MTC 表达，但奥曲肽治疗效果不佳，而最近帕瑞肽已证明对术后持续性 MTC 具有抗增殖作用。

本研究的目的是测试奥曲肽和帕瑞肽对 TT 细胞系以及原代 MTC 培养细胞中 MTC 细胞增殖、细胞周期蛋白表达、MAPK 活化、细胞凋亡、降钙素分泌、迁移和侵袭的影响。我们的结果表明，奥曲肽和帕瑞肽都降低了 TT 细胞增殖（-35.2±12.1%，p<0.001，和 -25.3±24.8%，p<0.05，在 10 ^-8M），同时抑制 ERK 磷酸化和细胞周期蛋白 D1 表达。这种细胞抑制作用伴随着促凋亡作用，caspase3/7 活性增加了 1.5 倍。此外，奥曲肽和帕瑞肽均抑制细胞迁移（分别为 -50.9±11.3%，p<0.01 和 -40.5±17%，p<0.05）和侵袭（-61.3±35.1%，p<0.05 和 -49.7± 18%，分别为 p<0.01）。未观察到对降钙素分泌的影响。然后我们尝试将这些观察结果扩展到原代文化（n=5）。奥曲肽和/或帕瑞肽在 5 个肿瘤中的 3 个中有效减少细胞增殖，并在 3 个 MTC 中的 1 个中诱导细胞凋亡。在所有测试的 MTC 中，奥曲肽和帕瑞肽都能够减少细胞迁移。SST2、SST3 和 SST5 在所有 MTC 中均有表达，与野生型 MTC 相比，RET 突变的 MTC 中 SST2 的表达有增加的趋势。一致地，抑制 TT 细胞中突变的 RET 降低了 SST2 表达。

总之，我们证明了奥曲肽和帕瑞肽抑制了一部分 MTC 的细胞增殖和侵袭性，支持它们在控制肿瘤生长中的潜在用途。