Effect Of Magnetic Induction Thermochemotherapy On Human Colon Cancer SW480 Cells

The U.S.Food and Drug Administration（FDA）recognized hyperthermia as a clinical treatment for cancer in 1985,and since then hyperthermia has entered the field of cancer treatment.In cancer treatment programs,hyperthermia is often used as an auxiliary means of surgery,chemotherapy,radiotherapy and so on.Based on the difference of thermal sensitivity between normal tissue and tumor focus area,hyperthermia uses physical energy to heat the tumor focus area to kill cancer cells,which has the advantage of less damage to normal tissue.Magnetic induction hyperthermia is a kind of targeted hyperthermia therapy.Its principle is that magnetic materials implanted in the tumor focus area will only warm up the local area under the external magnetic field,which reduces the damage to the non-lesion area.Thermo-chemotherapy is a commonly used cancer treatment program.It absorbs the advantages of thermotherapy and chemotherapy,makes up for their shortcomings,and greatly improves the curative effect of cancer.Thermo-chemotherapy perfusion is the most commonly used combination therapy in clinic.In this study,micron magnetic microspheres and human colon cancer SW480 cells were selected as experimental materials to explore the effects of magnetic induction hyperthermia combined with oxaliplatin or 5-fluorouracil（5Fu）on the proliferation and apoptosis of SW480cells.The effects of magnetic induction hyperthermia combined with chemotherapy and its anti-tumor biological mechanism were investigated by studying the expression of related proteins and genes.The main results and conclusions are as follows:1.The experiments of temperature rise and cell compatibility of magnetic microspheres show that magnetic microspheres have good temperature rise,and can raise the temperature to above 45 C within 30 minutes,which meets the needs of hyperthermia.Toxicity experiments prove that magnetic microspheres are less toxic,which further confirms the potential of magnetic microspheres as a medium of magnetic induction hyperthermia.2.MTT（thiazolidine blue）results showed that the cell viability of normal group was significantly different from that of oxaliplatin,5Fu,hyperthermia,hyperthermia+oxaliplatin and hyperthermia+5Fu groups.By calculating the Q value of combination index,hyperthermia combined with chemotherapy had synergistic effect on SW480 cells.3.Apoptotic analysis showed that compared with normal group,oxaliplatin group,5Fu group,hyperthermia group,hyperthermia+oxaliplatin group and hyperthermia+5Fu group,the apoptotic rate of SW480 cells in treatment group was consistent with the cell viability detected by MTT test.4.Cell cycle studies show that hyperthermia,hyperthermia+oxaliplatin and hyperthermia+5Fu groups can make cells stagnate in S phase.Oxaliplatin and 5Fu break down the cell cycles in G₂/M and G₀/G₁ phase,respectively.5.Protein expression studies showed that hyperthermia,5Fu,oxaliplatin,hyperthermia+oxaliplatin and hyperthermia+5Fu could adjust the expression of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2.The combination of hyperthermia and chemotherapy could significantly increase the expression of Bax protein in SW480 cells and reduce Bcl-2.6.Quantitative gene expression showed that after treatment with 5Fu,oxaliplatin,hyperthermia,hyperthermia+oxaliplatin and hyperthermia+5Fu,the accumulation of Bax and Bcl-2 gene changed.Bax was up-regulated and Bcl-2 was down-regulated.The hyperthermia+oxaliplatin group and the hyperthermia+5Fu group was most significant,indicating that mitochondrial pathway was involved in apoptosis.