Experiment And Clinical Study On Colon Cancer Treated By Mild Hyperthermia Combined With Chemotherapy

Colon cancer is one of the three leading causes of cancer mortality worldwide. Surgery combined with radiation is considered as the most effective method of treating colorectal cancer though that has no obvious effect on advanced colon cancer. 5-FU is still the basic chemotherapeutic regent in treating advanced colorectal cancer. While oxaliplatin added to LV/5-FU was shown to take more effect on the cancer treatment. Though it is , The survival rate of colon cancer has not significantly improved. Which may be due to the drug tolerance and the chemotherapeutic toxicity. An admirable protocol for treating advanced colorectal cancer is needed.One way to treat the cancer is thermotherapy, which should heat the tumor tissue to 40℃ and 45℃ as therapeutic temperature and last a certain time until destroying the tumor but not damaging the normal tissue. Thermotherapy is applied as an adjunctive therapy in cancer treatment. Thermotherapy has been called " green therapeutics" because It may improve the chemotherapeutic sensitivity to cancer and reduce their side effects. However, it is difficult to reach the tumor deep tissue temperature to over 43 ℃ by conditional thermotherapy, which is due to its different heat distribution in body tissue, on the other hand, more studies had demonstrated that human tumor cells will develop heat tolerance after heating with longtime. It was shown that at temperatures between 41℃ and 42 ℃, human tumor cells may be more sensitive to the mild thermotherapy and less tolerance than that of rodent tumor cells. According to the studies, we investigate the effects and mechanisms of mild thermotherapy on human colon cancer to demonstrate its feasibility of clinical practice.Experimental studyEffects of the mild thermotherapy combined with chemotherapy on Human Colon Cancer RKO cell LineObjective: To investigate the effects and mechanisms of mild thermotherapy combined with chemotherapy on human colon cancer cell line (RKO). Methods: The experiment was performed with RKO cell line and designed by hierachical classification. Groups were divided by two factors: seven different duration of the mild thermotherapy( 0min, 30min, 1hr, 2hr, 3hr, 4hr, 5hr) and four different chemotherapeutic drugs combination(blank control group, 5-Flurouracil (5-FU), oxaliplatin (L-OHP), 5-FU+L-OHP). The mild thermotherapy and chemotherapy was treated at the same time. For mild thermotherapy, tightly caped flasks with RKO cells suspension were submerged in heat water bath(41.5℃) for different time. The cytotoxic effects were assessed by MTT method after 48hr treatment. The cell apoptosis was detected by flow cytometry using Annexin V/PI doulble labeling reagent after0hr, 6hr, 12hr, 24hr, 36hr,48hr treatment. The morphology of cell apoptosis was observed by microscopy and inverted microscope. Results: There is no obvious cytotoxic effects on RKO cells heated with 41.5℃ after 1hr. After heating over 1hr or longer time, there were high inhibit rate (IR) in single heated group, L-OHP group or 5-FU+L-OHP group. But the IRs was no statistical difference in 5-FU groups. Mild thermotherapy after 1hr combined with chemotherapy could obviously increase the cell cytotoxicity. Typical morphology of RKO cells apoptosis was observed after treating with mild thermotherapy at 41.5℃ for 2hrs. The cell apoptosis rate was increased significantly during the time of the first day of the thermotherapy, and it was decreased during 24hr and 48hr after treatment which could be explained that more necrotic cells were seen at that time. Conclusion: There was obvious cytotoxic effect on RKO cells treated with mild thermotherapy at 41.5℃ after more than one hour, typical morphology of cell apoptosis was observed. Mild thermotherapy for more than one hour combined with L-OHP or 5-FU+L-OHP can significantly inhibit the cell growth but not that of combined with 5-FU.Clinical studies:Effect of inner field regional mild thermotherapy combined with chemotherapy on advanced colorectal cancerObjective:...