title: Wild-type phosphatase and tensin homolog deleted on chromosome 10 improved the sensitivity of cells to rapamycin through regulating phosphorylation of Akt in esophageal squamous cell carcinoma.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most frequently diagnosed cancers in China, but the etiology and mode of carcinogenesis of this disease remain poorly understood. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), as a negative regulator of Akt/mTOR pathway, frequently mutates or is inactive in many cancers. Although mTOR has been thought a promising cancer therapeutic target, the sensitivity of tumor cells to rapamycin was still to be revaluated. In this study, we measured the effects of rapamycin on cell proliferation and phosphorylation of Akt in ESCC cells with varying degrees of differentiation. And then, the relationship between PTEN status and the sensitivity of cells to rapamycin was investigated in EC9706 cells with or without wild-type PTEN in vitro and in vivo. The results demonstrated ESCC cells with poor differentiation were insensitive to rapamycin of high concentration and rapamycin obviously promoted the phosphorylation of Akt in these cells, but it had no obvious effects on p-Akt in cells with well differentiation. Also, we showed that wild-type PTEN improved the sensitivity of poor differentiation cells to rapamycin through inhibiting phosphorylation of Akt in vitro and in vivo. This study explored the possible molecular mechanism of some ESCC cells insensitive to rapamycin and provided a measure for treating ESCC patients with PTEN inactivation using mTOR inhibitors.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Zhengzhou University, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Zhengzhou University, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Zhengzhou University, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Zhengzhou University, China.
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.affiliation: Oncology Department, People's Hospital of Henan Province, China.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Zhengzhou University, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Zhengzhou University, China.|New Drug Research and Development Centre of Zhengzhou University, Zhengzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Zhengzhou University, China.|New Drug Research and Development Centre of Zhengzhou University, Zhengzhou, China.
authors.forename: G
authors.initials: G
authors.lastname: Hou
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000187:drug effects / Q000235:genetics*; D010597:Pharmacogenetics; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D020123:Sirolimus
keywords: Akt; PTEN; esophageal squamous cell carcinoma; rapamycin