title: More antitumor efficacy of the PI3K inhibitor GDC-0941 in breast cancer with PIK3CA mutation or HER2 amplification status in vitro.
abstract: PIK3CA is probably the most commonly mutated kinase in several malignant tumors. Activation of class I phosphatidylinositol 3' kinase (PI3K) regulates tumor proliferation, survival, etc. This study sought to identify whether the pan-inhibitor has more antitumor efficacy in breast cancer cells with PIK3CA Mutation or HER2 amplification than basal-like cancer cells. The proliferation of breast cancer cells was measured by MTT assay in the presence of GDC-0941. Afterwards, we determined the visible changes in signaling in the PI3K/AKT/mTOR pathway. Finally, we examined GDC-0941 effects on cell cycle, apoptosis and motility. GDC-0941 exhibited excellent inhibition on three cell lines with PIK3CA mutation or HER2 amplification. In addition, GDC-0941 resulted in decreased Akt activity. GDC-0941 downregulated the key components of the cell cycle machinery, such as cyclin D1, upregulated the apoptotic markers and inhibited cell motility on three cell lines with PIK3CA Mutation or HER2 amplification. Antitumor activity of GDC-0941 treatment amongst tumor cell lines with PIK3CA mutation and HER2 amplification may have clinical utility in patients with these oncogenic alterations.
authors.affiliation: Department of Pathology, Jingmen First People's Hospital, Jingmen, People's Republic of China. zhengjie9803@gmail.com
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Public Health, Duodao People's Hospital, Jingmen, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Jingmen First People's Hospital, Jingmen, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Pathology, Jingmen First People's Hospital, Jingmen, People's Republic of China.
authors.forename: Xianjin
authors.initials: X
authors.lastname: Zou
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D007202:Indicators and Reagents; D009154:Mutation / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D058534:Class I Phosphatidylinositol 3-Kinases; D007191:Indazoles; D007202:Indicators and Reagents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D013449:Sulfonamides; C532162:2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human