| Objective: Primary liver cancer (Primary liver cancer) is the most commonmalignant tumors of the digestive system, accounting for5.6%of all the totalnumber of cancers. More than50%of liver cancer worldwide occur in China,the mortality rate ranks first two malignancies, serious threat to life and healthof the people. Radiation therapy is the case in organ preservation treatmentused to control a local tumor, has become an important means of treatment ofliver cancer. Radiotherapy alone is only part of the radiation-sensitive tumorshave a good effect, but there are still a variety of tumors to radiation is notvery sensitive. Radiation sensitizer can increase the sensitivity of tumor cellsto radiation and radiation killing rate of tumor cells, and enhance the efficacyof radiotherapy has become an important research topic in cancer radiotherapy.hematoporphyrin),1,3,5,8,-tetramethyl-2,4-(α-hydroxyethyl)-Porphine-6,7-twopropionic acid (C34H38N4O6), was approved by SFDA country a class ofchemical drugs hematoporphyrin derivative. The drugs have a special affinityfor tumor tissue, chemicals can be selectively concentrated in the site ofaction,48h after application of the concentration in the tumor tissue is10-30times the normal tissue than in normal tissue extended drain48-72h, or240hor more. In addition, hematoporphyrin of soluble in water, ease ofadministration,the electromagnetic wave can be excited to play a role inkilling cancer cells and vital organs without apparent toxicity, are expected tohave better tumor radiosensitization effect. In this experiment with H22hepatoma cells Kunming mouse mod el for the study, r es ear chhematoporphyrin of joint anti-tumorefficacy of different doses of radiotherapyprograms and radiosensitization effect, set the control group,hematoporphyrin group, radiotherapy group, a combination therapy group,radiotherapy group2, group2combination therapy, radiotherapy three groups combined treatment group3of8groups in group3of8groups intumor volume, q value and sensitizing factor analysis, tumor weightinhibition rate of mice survival, pathology research comparing HE staining,apoptosis, treatment side effects and so on. hematoporphyrin effective way toobserve the test of inhibition of liver cancer radiation sensitizing effect, thedegree of sensitization, and the combination of the two methods andpreliminary exploration sensitization mechanisms, with a view to exploringthe photosensitizer radiosensitization and find malignant new ways of treatingcancer provide a theoretical basis.Method:1Create H22hepatoma cells in mice xenograft model and experimental groups:divided randomly divided into control group A (Control), Bgrouphematoporphyrin (Hp), C radiotherapy group (Rt1), D1combination therapygroup (Hp+Rt1), E radiotherapy group2(Rt2), F2combination therapygroup (Hp+Rt2), G radiotherapy group3(Rt3), H3combination therapygroup (Hp+Rt3)8groups.2Every other day mouse xenograft tumor diameter measurements to calculatethe tumor volume and tumor growth inhibition rate and growth curve;analysis sensitizing and sensitizing factor q values observed inhibitorysensitizing effect.3After the first14days the mice were sacrificed part of said tumor weight,tumor inhibition rate calculation.4Remaining mice were observed for quality of life and survival, the survivalcurves plotted to calculate life span.5Mouse xenograft tumor tissue HE staining microscope apoptotic necrosis.6Flow cytometric analysis of tumor tissue in each group apoptosis and cellcycle distribution.7Calculate the thymus index and spleen index were observed in miceimmunized situation.8Statistical analysis: SPSS13.0software for each set of data for statisticalanalysis. Outcome measures between the groups were compared using ANOVA test for multiple comparisons between groups using LSD-t test,tumor-bearing mice in each group were analyzed using Kaplan-Meier survivalmethod. Each test are P <0.05was considered statistically significant.Results：1H22hepatoma cells grown in Kunming mice tumor formation rate of100%.2Mice transplanted tumor volume changes and tumor growth inhibitionrate:Before treatment, the average initial tumor volume (852.6656±70.91993)mm3, ANOVA was no significant difference (F=0.911, P=0.503), aftertreatment4Days tumor volume differences between the groups (F=7.749, P=0.000), the first14days of each group tumor volume analysis of variancestatistically significant (F=277.924,P=0.000). Control group, hematoporphyringroup, hematoporphyrin radiotherapy group, the combination therapy group,radiotherapy group2, group2combination therapy, radiotherapy three groupscombined treatment group314th day of tumor growth inhibition rateswere:0,0.58%,24.48%,29.67%,34.83%,49.82%,49.15%,52.12%.3q values and sensitizing factor analysis: each combined treatment groupwere mean q>1, with the combination therapy group, the average value of q2maximum (1.5216±0.12940); each combined treatment group were morethan one EF, EF largest combined treatment group2(1.7225).4In each group and the tumor weight inhibition rate of tumor: tumor weightvariance analysis showed a statistically significant difference between groups(F=127.352,P=0.000). C o n t r o l g r o u p, h e m a t o p o r p h y r i n g r o u p,radiotherapy group, the combination therapy group, radiotherapy group2,group2combination therapy, radiotherapy three groups combined therapy oftumor inhibition rate of the three groups were:0,0.488%,22.83%,27.96%,32.60%,48.962%,48.31%,49.94%.5Survival of tumor-bearing mice: In addition to hematoporphyrin group, eachof the treatment groups could prolong the survival time of mice, the miceimproved quality of life, survival analysis of variance showed a statisticallysignificant difference between groups (F=75.511,P=0.000), combinedtreatment group2survive the longest, highest rate of life extension. 6Tumor pathology observed: Hematoporphyrin with the control group andgroup compared to the treatment groups were to reduce the number of tumorcells, the cell structure of local red dye no increase in performance. In themost obvious combination therapy group2, the largest number of tumor cellnecrosis, necrosis Range Max.7cell apoptosis and cell cycle distribution: In addition to hematoporphyringroup, the apoptosis rate increased each treatment group, the difference wasstatistically significant (P=0.000), the combination therapy group2apoptotichighest peak. Each share of the combined treatment group showed adecreasing trend G0/G1phase of the cell, but little change in the proportion ofS phase cells showed a decreasing trend, G2/M phase cells was significantlyincreased tendency to combination therapy group2most significant.8In each group of mice thymus index, spleen index detection: In addition tohematoporphyrin group, each of the treatment groups spleen index and thymusindex has declined compared with the control group, and with the increase ofradiation dose decreasing trend, but the combination therapy group and eachthe same dose radiotherapy group difference was not statistically significant.Conclusion: Hematoporphyrin(15mg/Kg) combined with different doses ofradiotherapy (5Gy,10Gy,15GyX line) Can be different degrees of H22hepatoma mice inhibitory efficiency, radiosensitization occurred; are differentThe degree of improvement in survival in mice; radiosensitivity by promptingcells to enter the highest G2/M phase, Promote tumor cell apoptosis andnecrosis; compared with radiotherapy alone, without lowering immunity inmice Side effects. Considering the treatment and quality of life from theperspectives of the photosensitizer derivatives hematoporphyrin10GyX linewith the most advantage of synchronous radiotherapy, radiotherapy alone canimprove the sensitivity1.7225times. |
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