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慢病毒介导的PLCγ1基因短发夹RNA抑制人胃腺癌的肿瘤生长和转移。

Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma.

作者信息

Zhang Bingchang, Wang Fen, Dai Lianzhi, Cai Heguo, Zhan Yanyan, Gang Song, Hu Tianhui, Xia Chun, Zhang Bing

机构信息

School of Medicine, Xiamen University, Fujian, 361102, China.

Zhongshan Hospital, Xiamen University, Fujian, 361004, China.

出版信息

Oncotarget. 2016 Feb 16;7(7):8043-54. doi: 10.18632/oncotarget.6976.

Abstract

Targeted molecular therapy has gradually been a potential solution in cancer therapy. Other authors' and our previous studies have demonstrated that phosphoinositide-specific phospholipase γ (PLCγ) is involved in regulating tumor growth and metastasis. However, the molecular mechanism underlying PLCγ-dependent tumor growth and metastasis of gastric adenocarcinoma and whether PLCγ may be a potential target for tumor therapy in human gastric adenocarcinoma are not yet well determined. Here, we investigated the role of PLCγ inhibition in tumor growth and metastasis of human gastric adenocarcinoma using BGC-823 cell line and a nude mouse tumor xenograft model. The results manifested that the depletion of PLCγ1 by the transduction with lentivirus-mediated PLCγ1 gene short-hairpin RNA (shRNA) vector led to the decrease of tumor growth and metastasis of human gastric adenocarcinoma in vitro and in vivo. Furthermore, the Akt/Bad, Akt/S6, and ERK/Bad signal axes were involved in PLCγ1-mediated tumor growth and metastasis of human gastric adenocarcinoma. Therefore, the abrogation of PLCγ1 signaling by shRNA could efficaciously suppress human gastric adenocarcinoma tumor growth and metastasis, with important implication for validating PLCγ1 as a potential target for human gastric adenocarcinoma.

摘要

靶向分子疗法已逐渐成为癌症治疗的一种潜在解决方案。其他作者以及我们之前的研究表明,磷脂酰肌醇特异性磷脂酶γ(PLCγ)参与调节肿瘤的生长和转移。然而,PLCγ依赖性胃腺癌肿瘤生长和转移的分子机制以及PLCγ是否可能成为人类胃腺癌肿瘤治疗的潜在靶点尚未完全明确。在此,我们使用BGC-823细胞系和裸鼠肿瘤异种移植模型研究了抑制PLCγ在人类胃腺癌肿瘤生长和转移中的作用。结果表明,通过慢病毒介导的PLCγ1基因短发夹RNA(shRNA)载体转导使PLCγ1缺失,导致体外和体内人类胃腺癌肿瘤生长和转移减少。此外,Akt/Bad、Akt/S6和ERK/Bad信号轴参与了PLCγ1介导的人类胃腺癌肿瘤生长和转移。因此,shRNA消除PLCγ1信号可有效抑制人类胃腺癌肿瘤生长和转移,这对于验证PLCγ1作为人类胃腺癌的潜在靶点具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e52/4884974/7d1031f83b5b/oncotarget-07-8043-g001.jpg

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