The Influence Of EIF4E On The Xenograft And Chemosensitivity Of Human Esophageal Squamous Carcinoma In Nude Mice

ObjectiveTo observe the influence of eIF4E on the growth rate of esophageal squamous carcinoma cells and the sensitivity to cisplatin chemotherapy in vivo using xenograft nude mice models.Methods1. Three different kind of cells,including untreated esophageal squamous carcinoma EC9706cells, pre-established eIF4E silenced EC9706cells and eIF4E overexpressed EC9706cells were recovered and cultured.2. We observe the general case of nude mice and subcutaneous xenografts, and record growth of the transplanted tumor and draw tumor growth curve of each group. Then we strip tumor tissues timely, after that weighing the tumor tissues weight respectively.3.Identify the eIF4E expression in transplanted tumor tissues by qRT-PCR, Western Blot and immunohistochemistry for each group.Results1.We have successfully established the tumor model in nude mice by using untreated esophageal squamous carcinoma EC9706cells and pre-established eIF4E silenced EC9706cells and eIF4E overexpressed EC9706cells, which has been detected in pathology by HE staining. This model has similar pathological features to human esophageal squamous carcinoma.2. The average time to formed a tumor of untreated EC9706group in nude mice is5days, while the average time to formed a tumor of eIF4E silenced EC9706group in nude mice is7days and the average time to formed a tumor of eIF4E overexpressed EC9706group in nude mice is4days. After cisplatin treatment, the volume of subcutaneous transplanted tumors in untreated EC9706group is1341.49±333.43mm3, the tumor weight is1.3745±0.3685g, while the volume of subcutaneous transplanted tumors in eIF4E silenced EC9706group is658.92±472.12mm3, the tumor weight is0.6083±0.2817g, differences has statistics significance(P<0.05). In addition, the volume of subcutaneous transplanted tumors in eIF4E overexpressed EC9706group is2246.75±814.25mm3, the tumor weight is1.9790±0.4342g, differences has statistics significance(P<0.05). After normal saline treatment, the volume of subcutaneous transplanted tumors in untreated EC9706group is2066.51±543.48mmj, the tumor weight is2.3671±0.3847g, while the volume of subcutaneous transplanted tumors in eIF4E silenced EC9706group is1416.27±396.59mm3, the tumor weight is1.2363±0.4582g, differences has statistics significance(P<0.05). In addition, the volume of subcutaneous transplanted tumors in eIF4E overexpressed EC9706group is3432.61±878.15mm3, the tumor weight is2.9912±0.4201g, differences has statistics significance(P<0.05).3. The six groups are untreated EC9706cells inoculation with cisplatin intervention, untreated EC9706cells with saline control, eIF4E silenced EC9706cells inoculation with cisplatin intervention, eIF4E silenced EC9706cells inoculation with saline control, eIF4E overexpressed EC9706cells inoculation with cisplatin intervention and eIF4E overexpressed EC9706cells with saline control.There transplanted tumor tissue relative expression of eIF4E mRNA were detected by qRT-PCR, and the result are:3.7440±0.80317,3.9417±1.15404,1.0767±0.10443,1.0883±0.10323,15.8250±3.43139,5.8533±2.82740.Western Blot detect eIF4E protein expression in each gr oup, the results are0.7515±0.14425,0.7998±0.18601,0.5391±0.15702,0.5394±0.17053,1.0565±0.23503,1.1386±0.29452.Immunohistoche mical staining detect eIF4E protein expression in each group, the immunohistochemical staining scores are:2.4000±1.14018,2.1667±0.75277,1.0000±0.89443,1.0000±0.89443,6.6667±3.01109,7.0000±3.46410.The above test results for statistical analysis indicate that comparing with untreated EC9706cells inoculation with cisplatin intervention, the two groups that eIF4E silenced EC9706cells inoculation with cisplatin intervention and eIF4E overexpressed EC9706cells inoculation with cisplatin intervention have obviously difference (P<0.05). Comparing with untreated EC9706cells inoculation with saline control, the two groups that eIF4E silenced EC9706cells inoculation with saline control and eIF4E overexpressed EC9706cells inoculation with saline control have obviously difference (P<0.05). Untreated EC9706cells inoculation with cisplatin intervention and untreated EC9706cells with saline control, eIF4E silenced EC9706cells inoculation with cisplatin intervention and eIF4E silenced EC9706cells inoculation with saline control, eIF4E overexpressed EC9706cells inoculation with cisplatin intervention and eIF4E overexpressed EC9706cells with saline control, there was no significant difference (P>0.05).Conclusions1. We have successfully established human esophageal squamous carcinoma xenograft nude mice models by untreated esophageal squamous carcinoma EC9706cells, pre-established eIF4E silenced EC9706cells and eIF4E overexpressed EC9706cells.2. Silencing the expression of eIF4E inhibited the growth rate of ESCC. eIF4E overexpression accelerated the growth rate of ESCC.3. Silencing the expression of eIF4E improved the chemosensitivity to cisplatin on esophageal squamous carcinoma cell. Conversely, eIF4E overexpression reduced the chemosensitivity to cisplatin.