title: Phosphatidylinositol 3-kinase-C2β inhibits cisplatin-mediated apoptosis via the Akt pathway in oesophageal squamous cell carcinoma.
abstract: A major problem in treating oesophageal squamous cell carcinoma (ESCC) with cisplatin is the development of drug resistance. In order to determine whether phosphatidylinositol 3-kinase (PI3K)-C2β (encoded by the PIK3C2B gene) reduced the sensitivity of ESCC to cisplatin,  transfected Eca109 cells that overexpressed PIK3C2B were produced. Additionally, PI3K-C2β-siRNA was used to silence endogenous PI3K-C2β in EC9706 cisplatin-resistant cells. The relationship between PIK3C2B  expression and clinicopathological characteristics was also  investigated in samples from 61 patients. The overexpression of PIK3C2B in Eca109 cells significantly inhibited cisplatin-induced apoptosis and cleavage of caspase-3. Knockdown of PI3K-C2β enhanced cisplatin-induced apoptosis in EC9706 cells. PIK3C2B expression was associated  with an increased level of phosphorylated Akt. Based on the tumour samples, expression of PIK3C2B was associated with tumour metastasis and in vitro assay suggested that it mediated cell migration. These results indicated that PI3K-C2β, via the Akt signalling pathway, might  play a key role in cisplatin resistance and that targeting this pathway might be useful in treating cisplatin-resistant tumours.
authors: Department of Oncology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors: Z
authors: Z
authors: Liu
authors: C
authors: C
authors: Sun
authors: Y
authors: Y
authors: Zhang
authors: Z
authors: Z
authors: Ji
authors: G
authors: G
authors: Yang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D058541:Class II Phosphatidylinositol 3-Kinases; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D058541:Class II Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; C502616:PIK3C2B protein, human