Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma.
Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma.
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慢病毒介导的PLCγ1基因短发夹RNA抑制人胃腺癌肿瘤生长和转移
DOI：
10.18632/oncotarget.6976
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发表时间：
2016-02-16
期刊：
影响因子：
--
通讯作者：
Zhang B
中科院分区：
文献类型：
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作者：
Zhang B;Wang F;Dai L;Cai H;Zhan Y;Gang S;Hu T;Xia C;Zhang B
靶向分子治疗已逐渐成为肿瘤治疗的一个潜在解决方案。其他作者和我们前期的研究表明，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依赖的胃腺癌肿瘤生长和转移的分子机制以及PLCγ是否可能成为胃腺癌治疗的潜在靶点尚未得到很好的确定。本研究采用人胃腺癌BGC-823细胞株和裸鼠移植瘤模型，研究PLCγ抑制剂在人胃腺癌生长和转移中的作用。结果表明，慢病毒介导的PLCγ1基因短发夹状RNA（shRNA）载体转导PLCγ1后，可抑制人胃腺癌细胞的生长和转移。Akt/Bad、Akt/S6和ERK/Bad信号轴参与PLCγ1介导的人胃腺癌生长和转移。因此，通过shRNA废除PLCγ1信号通路可以有效抑制人胃腺癌肿瘤的生长和转移，这对于验证PLCγ1作为人胃腺癌潜在靶点具有重要意义。
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.