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.
Highlights
Gastric cancer is a highly malignant tumor with a complex etiology that results in many patients being diagnosed after the disease has reaches an advanced stage or in the occurrence of relapse after curative surgery
These results indicate that lentivirus-mediated PLCγ1 short-hairpin RNA (shRNA) suppress cell proliferation of human gastric adenocarcinoma cells
Our findings indicate that the depletion of PLCγ1 by the transduction with lentivirus-mediated PLCγ1 shRNA vector led to the suppression of tumor growth and metastasis in human gastric adenocarcinoma in vitro and in vivo
Summary
Gastric cancer is a highly malignant tumor with a complex etiology that results in many patients being diagnosed after the disease has reaches an advanced stage or in the occurrence of relapse after curative surgery. The targeted molecules include signaling molecules, growth factor receptors and microRNAs [2, 3]. Phosphoinositide-specific phospholipase γ (PLCγ) is activated downstream of many receptor tyrosine kinases and growth factors [4]. PLCγ induces hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to form the second messengers diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), which in turn activate a number of signaling pathways to regulate the metabolism in many cell types, including cancer cells [4,5,6,7]. Depletion of PLCγ expression or inhibition of its activity increases cisplatin-induced apoptosis and suppresses the invasive ability of RhoGDI2-overexpressing SNU- 484 gastric cancer cells [9]. PLCγ activity appears to support both tumor growth and metastasis
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