Department of Nursing, Jiangsu College of Nursing, Huaian, Jiangsu 223300, P.R. China.
Oncol Rep. 2018 Sep;40(3):1243-1250. doi: 10.3892/or.2018.6526. Epub 2018 Jun 26.
Kank1, an important member of the Kank gene family, plays an important role in the development of many malignant tumors. As a brand new tumor-suppressor gene, the expression of Kank1 gene has been revealed to be downregulated or absent in many malignant tumors. However, there is no study concerning the specific role of Kank1 in the development and progression of lung cancer. In the present study, we found that the Kankl gene was significantly downregulated in human lung cancer and lung cancer cells. When the Kankl gene was upregulated, we found that the proliferation of lung cancer cells was significantly inhibited, the cells were arrested in the G0/G1 phase, the apoptosis of cells was observed, the expression of the caspase family of genes was altered with mainly the activation of caspase-3 and -9, and Bcl-2/Bax ratio was significantly imbalanced. In addition, we also found that upregulation of the Kankl gene resulted in the inhibition of tumor cell invasion and metastasis. Concurrently, in vivo nude mice experiments also confirmed that upregulation of Kank1 expression led to reduced tumor formation in nude mice and significantly reduced tumor volume. These results revealed that upregulation of the Kankl gene inhibited the progression of lung cancer both in vitro and in vivo, and its mechanism was closely related to cell apoptosis as well as tumor invasion and metastasis.
Kank1 是 Kank 基因家族的重要成员，在许多恶性肿瘤的发生发展中发挥着重要作用。作为一个全新的抑癌基因，Kank1 基因的表达已被揭示在许多恶性肿瘤中下调或缺失。然而，目前尚无关于 Kank1 在肺癌发生和发展中具体作用的研究。在本研究中，我们发现 Kankl 基因在人肺癌及肺癌细胞中显著下调。当上调 Kankl 基因时，我们发现肺癌细胞的增殖受到明显抑制，细胞被阻滞在 G0/G1 期，观察到细胞凋亡，细胞中 caspase 家族基因的表达发生改变，主要表现为 caspase-3 和 caspase-9 的激活，Bcl-2/Bax 比值明显失衡。此外，我们还发现上调 Kankl 基因可抑制肿瘤细胞的侵袭和转移。同时，体内裸鼠实验也证实上调 Kank1 表达可导致裸鼠肿瘤形成减少，肿瘤体积明显缩小。这些结果表明，上调 Kank1 基因可抑制肺癌在体内外的进展，其机制与细胞凋亡以及肿瘤侵袭和转移密切相关。
