Wu Yan, Yuan Miaomiao, Su Wenbin, Zhu Miaolin, Yao Xiaoyuan, Wang Ying, Qian Hai, Jiang Lu, Tao Yan, Wu Min, Pang Ji, Chen Yongchang
Department of Physiology, School of Medicine, Jiangsu University. 301 Xuefu Road; and The Central Laboratory, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212013, China.
Department of Physiology, Jiangsu University, Zhenjiang, China.
Ther Adv Med Oncol. 2018 Feb 1;10:1758834017751635. doi: 10.1177/1758834017751635. eCollection 2018.
Type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) is a membrane-anchored enzyme expressed mainly in the intestinal mucosa and the brain, and is associated with various physiological or pathological processes. Upregulation of PKG II is known to induce apoptosis and inhibit proliferation and metastasis of cancer cells. The inhibitory effect of PKG II has been shown to be dependent on the inhibition of the activation of epidermal growth factor receptor (EGFR) and blockade of EGFR downstream signal transduction However, it remains unclear whether similar phenomena/mechanisms exist and whether these effects are independent of cGMP or cGMP analogues. In the present work, nude mice with transplanted orthotopic tumours were infected with adenovirus encoding cDNA of constitutively active PKG II mutant (Ad-a-PKG II) and the effect of constitutively active PKG II (a-PKG II) on tumour development was detected. The results showed that a-PKG II effectively ameliorated gastric tumour development through delaying the growth, inducing the apoptosis, and inhibiting the metastasis and angiogenesis. The effect was related to blockade of EGFR activation and abrogation of the downstream signalling cascades. These findings provide novel insight which will benefit the development of new cancer therapies.
II型环磷酸鸟苷（cGMP）依赖性蛋白激酶（PKG II）是一种主要在肠黏膜和大脑中表达的膜锚定酶，与多种生理或病理过程相关。已知PKG II的上调可诱导癌细胞凋亡并抑制其增殖和转移。PKG II的抑制作用已被证明依赖于对表皮生长因子受体（EGFR）激活的抑制以及对EGFR下游信号转导的阻断。然而，目前尚不清楚是否存在类似的现象/机制，以及这些作用是否独立于cGMP或cGMP类似物。在本研究中，将携带原位移植肿瘤的裸鼠感染编码组成型活性PKG II突变体cDNA的腺病毒（Ad-a-PKG II），并检测组成型活性PKG II（a-PKG II）对肿瘤发展的影响。结果表明，a-PKG II通过延缓肿瘤生长、诱导凋亡以及抑制转移和血管生成，有效改善了胃癌的发展。该作用与阻断EGFR激活和废除下游信号级联反应有关。这些发现提供了新的见解，将有助于开发新的癌症治疗方法。
