Research On Slow-cycling Tumor Cells

Despite considerable progress in the development of anticancer therapies, the mortality caused by cancer relapse and metastasis is still progressing which makes it the first cause of tumor-related death. Dormant or slow-cycling tumor cells are thought to be drug resistant and have the capability to survive from the traditional chemotherapy, thus become a source of tumor relapse and metastasis, and an obstacle to therapy. Although slow-cycling tumor cells play an important role in tumor relapse and metastasis, the research about slow-cycling tumor cells is deficient till now. In our research, we studied the biological characteristic of slow-cycling tumor cells and analyzed the therapeutic effect of the vaccine using inactivated slow-cycling tumor cells.First of all, fluorescent dye-stained CT-26cells were analyzed with flow cytometry, and the results demonstrated that there is a small population of slow-cycling tumor cells in the mouse colon carcinoma CT-26cell line. Then slow-cycling tumor cells were sorted using flow cytometry and injected into the mouse to determine their tumorigenicity. The results showed that compared with normal tumor cells, slow-cycling tumor cells had a higher tumorigenicity. And the results of side population analysis indicated that cancer stem cells were enriched in the slow-cycling tumor cells. The number of residual tumor cells was determined after culture in the medium with5-FU, and the percentage of slow-cycling tumor cell in residual tumor after drug treatment was analyzed. The results of above two experiments demonstrated the drug-resistant potential of slow-cycling tumor cells. All the findings provided good evidence for the hypothesis that slow-cycling and drug-resistant tumor cells are the source of tumor relapse and metastasis and an obstacle to therapy.To inhibit tumor recurrence and metastasis more effectively, therapy that selectively targets the slow-cycling tumor cells should be developed to complement the conventional therapies. What we found indicated that drug-treated and slow-cycling tumor cells induced a more intense immune response in vitro. Moreover, colon-tumor-bearing mice were immunized with inactivated slow-cycling CT-26cells to estimate vaccine efficacy, and the result showed that vaccination with inactivated slow-cycling tumor cells obviously reduced tumor volume and prolonged overall survival of tumor-bearing mice. Then we also did the preliminary research about the mechanism of the vaccination with slow-cycling tumor cells.In conclusion, our study provides good evidence for the hypothesis that slow-cycling tumor cells are the source of tumor relapse and metastasis, suggests that targeting of slow-cycling tumor cells application using immunotherapy is a possible treatment to complement traditional antitumor therapy.