title: Evaluation of HO-1 expression, cellular ROS production, cellular proliferation and cellular apoptosis in human esophageal squamous cell carcinoma tumors and cell lines.
abstract: Patients with esophageal squamous cell carcinoma (ESCC) have a poor prognosis. However, the related mechanisms are unclear, thus we investigated the expression of HO-1 in ESCC tissue and explored possible mechanisms of tumor progression. Expression of HO-1 was examined by immunohistochemistry in 143 ESCC tumors. The correlation of HO-1 with clinicopathological characteristics was also examined. Two human ESCC cell lines, TE-13 and Eca109 were studied. Silencing of cell line HO-1 by specific small interfering RNA (siRNA) was evaluated using real-time quantitative PCR. Cell line viability, apoptosis and intracellular levels of reactive oxygen species (ROS) after transfection were determined using MTT and flow cytometry, respectively. HO-1, Bax, Bcl-2 and A-caspase-3/-9 expression was evaluated using western blot analyses. We found that HO-1 was expressed in 58 of 143 ESCC tumors, mainly in the cytoplasm. There was a significant association between HO-1 expression and tumor grade (P<0.001). Knockdown of HO-1 expression in cell lines was associated with significantly decreased cellular proliferation (P<0.05) and a higher rate of apoptosis (P<0.001) 48 h after treatment. Treatment of the cell lines with the ROS inhibitor N-acetylcysteine abrogated this effect. Knockdown of HO-1 was associated with increased A-caspase-3 and -9 expression, but no change in Bax or Bcl-2 expression or Bax/Bcl-2 ratio was observed. Thus, the present study identified that ESCC tumors frequently expressed HO-1. Knockdown of HO-1 promoted apoptosis through activation of a ROS-mediated caspase apoptosis pathway.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jianghan, Wuhan, Hubei 430022, P.R. China.
authors.forename: Quan-Guang
authors.initials: QG
authors.lastname: Ren
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jianghan, Wuhan, Hubei 430022, P.R. China.
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Yang
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jianghan, Wuhan, Hubei 430022, P.R. China.
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Hu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jianghan, Wuhan, Hubei 430022, P.R. China.
authors.forename: Pin-Dong
authors.initials: PD
authors.lastname: Li
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jianghan, Wuhan, Hubei 430022, P.R. China.
authors.forename: Ye-Shan
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jianghan, Wuhan, Hubei 430022, P.R. China.
authors.forename: Qiu-Shuang
authors.initials: QS
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1