ABSTRACT
Cervical cancer is the second common cause of cancer deaths in women worldwide. Radioresistancy of cancer is a principal cause of treatment impairing. Inhibitor of apoptosis proteins (IAPs) widely block apoptosis against apoptotic stimuli, including current chemo- and radiation therapies. Apollon, a membrane of IAP, can support cells against apoptosis and is over expressed in some treatment-resistant cancer cells. The aim of this study was to evaluate the effects of apollon knockdown on induction of apoptosis and also its potential for enhancement of radiosensitvity on hela cells. plasmid encoding shRNA which has been confirmed its effect against apollon, transfected into hela cells. Consequent effects on the level of P53 , Bax and BAK analyzed by real time PCR. Apoptotic phenotype of transfected cells was monitored by Tunnel assay. Viability of hela cells after radiotherapy was analyzed by MTT assay. shRNA1 effectively increased transcription of p53, Bax and BAK and induced apoptosis phenotype of treated hela cells. Radiosensitivity of transfected cell was increased after knock-down of apollon obviously. Apollon knockdown induces apoptosis in hela cell . Also it can be as new molecular target for radio-sensitizing strategies in these cells. So, apollon can be a potentially considerable therapeutic object for cervical cancer.
ABSTRACT
Objective: p16INK4a is a tumor suppressor gene playing a critical role. Researches have indicated the gene to be altered in oral squamous cell carcinoma. Present studies have tried to assess the correlation between p16INK4a expression and INK4a locus mutation in relation to grades and stages of this tumor. Materials and Methods: Expression of p16INK4a was studied immunohistochemically in 58 oral squamous sell carcinoma samples and INK4a locus mutation was determined by polymerase chain reaction (PCR) and conformation sensitive gel electrophoresis (CSGE). Results: Expression of p16INK4a was higher in stage1 compared to stage 2, 3, and 4 (P = 0.234). The difference was not signifi cant in grade 1, 2, and 3 (P = 0.671). The average values of total score (TS) were signifi cantly higher in stage1 compared to stage 2, 3, and 4 (P = 0.035). The average values of complete score (CS) were higher in stage 1 compared to stage 2, 3, and 4 (P = 0.061). The research did not show a signifi cant correlation between lymph node involvement and p16INK4a expression (P = 0.491). It seems that 5.1% (3/58) of samples have mutation in INK4a locus. Conclusion: Loss of p16INK4a expression occurred in initial stages of oral squamous cell carcinoma. Evaluation of TS and CS for p16INK4a might be a useful clinical indicator concerning the tumor. However, gene mutation is believed to have minor rate of genetic alteration in carcinogenesis.