PIK3CA is critical for the proliferation, invasiveness, and drug resistance of human tongue carcinoma cells.
PIK3CA is an oncogene component of phosphatidylinositol 3-kinase (PI3K) signaling pathway and is associated with cell proliferation and carcinogenesis in a variety of human cancers. PIK3CA mutation is correlated with the aggressiveness of many epithelial cancers. And so PIK3CA is considered as a major oncogene in many human epithelial malignancies. However, its role in tongue carcinoma is unknown. We used lentiviral-mediated interfering short hairpin RNAs (shRNAs) to knock down PIK3CA expression in tongue carcinoma Tca8113 cells, and then we tested the cell proliferation by MTT assay and cell invasiveness by cell invasion assay. To examine whether PIK3CA is involved in the response of Tca8113 cells to an anticancer drug, cisplatin, we further performed cell death analysis by fluorescence-activated cell sorting (FACS). We found that knocking down PIK3CA led to slower cell growth and lessened cell invasiveness. In addition, PIK3CA downregulation increased Tca8113 cell death after cisplatin treatment, suggesting that PIK3CA downregulation might be helpful to increase the effects of some anticancer drugs. Moreover, in a mouse model of established large sized OSCC, we showed that suppression of PIK3CA markedly diminished tumorigenicity in vivo. To understand its molecular mechanism of action, we measured expression of phospho-PTEN (Ser380) and phospho-AKT (Ser473) by Western blot and found that suppression of PIK3CA inhibited OSCC growth through downregulation of p-PTEN and p-AKT. Our study highlights critical roles for PIK3CA in the tongue cancer, and suggests that PIK3CA gene might be considered as a therapeutic target for clinical tongue cancer.
Department of Oral & Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, PR China
Yu
Y
Chen
Qingyi
Q
Hou
Wangxiang
W
Yan
Jing
J
Luo
Dan
D
Chen
Zhiguo
Z
Liu
Shuqi
S
He
XueQiang
X
Ding
D000818:Animals; D000970:Antineoplastic Agents; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin; D058534:Class I Phosphatidylinositol 3-Kinases; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014062:Tongue Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*
D000970:Antineoplastic Agents; D002945:Cisplatin; D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D058539:Phosphatidylinositol 3-Kinase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C484760:PIK3CA protein, human; C494929:PTEN protein, human