Changes Of The Biological Characteristics On Invasion And Metastasis In Colorectal Cancer Cells After Concurrent Chemoradiotherapy And The Related Mechanism

Objective:In this study, we established the model of human colorectal cancer in vitro, studyed the changes of the biological behavior related to the invasion and metastasis of residual cancer cells after CRT. The key gene was screened by gene chip and then explored the possibility of modulating the biological behavior of residual cancer cells though interfering the expression of the key genes. This project would lay a foundation for further revealing the biological characteristics of residual colorectal cancer after neoadjuvant chemoradiotherapy and provide the scientific basis for improving the theuretic effect of colorectal cancer.Methods:1. The human colorectal cancer cells HCT116 and HT29 were treated with 4Gy 6MV X-ray and 10 umol / L 5-Fu in vitro to establish the residual cell model after concurrent chemoradiotherapy (HCT116CR, HT29CR).2. The migration and invasive ability of residual cells HCT116 CR and HT29CR were tested by Transwell migration and invasion assay.3. The expression of long non-coding RNA (IncRNA) in HCT116CR and HCT116 cells was detected using a gene chip.4. The siRNA method was apllied to block the expression of key genes in HCT16CR cell.QRT-PCR was also used to identify the effects of silencing the expression of these three IncRNAs in HCT116CR cells.5. Transwell migration and invasion assay were used again to detect the migration and invasion ability of siRNA-HCTl 16CR cells.Results:1. HCT116 and HT29 residual cell models were successfully established after four times of treatment with concurrent chemoradiotherapy.2. Transwell migration and invasive experiments found that the migration and invasive ability of the residual cells were increased compared with the original cell.3. The expression of lncRNAs related to the biological behavior of residual tumor cells after radiotherapy and chemotherapy was detected by biochip. And three key molecular targets were screened, PVT1, LINC00152 and MIR22HG.4. The siRNA succeed in silencing the expression of key molecular targets in HCT116CR cells. And the metastasis and invasion of siRNA-LINC00152 group were significantly reduced compared with the untreated group.Conclusion(s):1. The ability of invasion and metastasis of residual colorectal cancer cells increased and the biological behavior deteriorated after radiotherapy and chemotherapy.2. LINC00152 may be the key molecular target for modulating the changes in the biological characteristics of residual colorectal cancer cells after chemoradiotherapy.