Zhang Xue-Song, Hu Yan-Hua, Gao Hong-Yu, Lan Xiu-Wen, Xue Ying-Wei
Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China.
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Mol Med Rep. 2017 Aug;16(2):2318-2324. doi: 10.3892/mmr.2017.6791. Epub 2017 Jun 15.
Migration and invasion are both vital causes of mortality in patients with gastric cancer. Therefore, the inhibition of these tumour cell processes is of great importance in gastric cancer therapy. Activation of Notch has been reported in many cancers. The critical role of Notch and its regulation in tumourigenesis has been noted. Although the studies on Notch in the field of cancer have been performed extensively, the role of Notch1 signalling in gastric cancer requires further study. Inactivation of PTEN has been observed in the development of many malignant tumors, and loss of PTEN function has been implicated in tumorigenic processes. Notch acts as an upstream signalling pathway that regulates PTEN activities. However, the effect of Notch on invasion and metastasis in gastric cancer and the regulation of PTEN during this process remain poorly understood. In the present study, small interfering RNA (siRNA) was used to knock down Notch1 expression in gastric cancer cell lines SGC7901 and MKN74. The mRNA and protein expression of Notch1, PTEN, Akt and FAK were measured upon depletion of Notch1. phospho‑PTEN, phospho‑Akt and phospho‑FAK expression were measured using western blot analysis. Migration and invasion assays were also used after Notch1 depletion. Our results showed that the knockdown of Notch1 leads to the inhibition of cell invasion and metastasis of human gastric cancer cells SCG7901 and MKN74 in vitro. Compared to control and mock groups, PTEN activities were significantly promoted following depletion of Notch1, and the expression of Phospho‑Akt and Phospho‑FAK were downregulated. Taken together, our findings suggest that Notch1 could be used as a therapeutic target to inhibit cell invasion and migration in gastric cancer.
迁移和侵袭都是胃癌患者死亡的重要原因。因此，抑制这些肿瘤细胞过程在胃癌治疗中具有重要意义。许多癌症中都报道了Notch的激活。Notch及其调控在肿瘤发生中的关键作用已受到关注。尽管在癌症领域对Notch进行了广泛研究，但Notch1信号通路在胃癌中的作用仍需进一步研究。在许多恶性肿瘤的发生发展过程中都观察到了PTEN的失活，PTEN功能丧失与肿瘤发生过程有关。Notch作为上游信号通路调节PTEN活性。然而，Notch对胃癌侵袭和转移的影响以及在此过程中PTEN的调控仍知之甚少。在本研究中，使用小干扰RNA（siRNA）敲低胃癌细胞系SGC7901和MKN74中Notch1的表达。在Notch1缺失后，检测Notch1、PTEN、Akt和FAK的mRNA和蛋白表达。使用蛋白质印迹分析检测磷酸化PTEN、磷酸化Akt和磷酸化FAK的表达。在Notch1缺失后还进行了迁移和侵袭实验。我们的结果表明，敲低Notch1可导致人胃癌细胞SCG7901和MKN74在体外的细胞侵袭和转移受到抑制。与对照组和模拟组相比，Notch1缺失后PTEN活性显著增强，磷酸化Akt和磷酸化FAK的表达下调。综上所述，我们的研究结果表明，Notch1可作为抑制胃癌细胞侵袭和迁移的治疗靶点。
