Effects Of Implanted Radioactive I¹²⁵ Particles On Apoptosis And Expression Of PDCD4,PTEN,Beclin1 And P62 In Transplanted Tumor Cells Of Human Lung Adenocarcinoma In Nude Mice

Objective: To observe the proliferation and apoptosis of human lung adenocarcinoma xenografts in nude mice after implantation of I¹²⁵ seeds and the expression of apoptosis-related genes PDCD4,PTEN,autophagy-related Beclin1 gene and P62 protein.Methods:A total of 40 lung adenocarcinoma A549 cells were subcutaneously transplanted into nude mice.They were randomly divided into 4 groups,10 in each group,which were 0 m Ci group,0.6 m Ci group,0.8 m Ci group and control group.A radioactive particle was implanted into each group of nude mice xenografts.The radioactivity of each group was 0 m Ci,0.6 m Ci and 0.8 m Ci,respectively.The control group did not perform any operation.The growth of nude mice and transplanted tumors was observed,and tumors were measured every 4 days.The volume of the tumor was calculated by combining the mathematical formula,and the growth curve of the transplanted tumor was drawn.On day 35,these nude mice were sacrificed and tumors were examined:?1?conventional hematoxylin-eosin?HE?staining for pathological findings of transplanted tumor tissues;and?2?detection of apoptosis of tumor cells using deoxynucleosides Acid terminal transferase?Td T?-mediated d UTP nick end labeling method,and accurate measurement of apoptotic index;?3?Immunohistochemical S-P method was used to detect the expression of Ki-67 in transplanted tumor tissues of each group,and the proliferation index was calculated.Immunohistochemical method was used to detect the expression of PDCD4,PTEN,Beclin1 and P62 protein in transplanted tumor tissues of each group.Results:?1?Lung adenocarcinoma A549 cells formed small nodular xenografts at the inoculation site 5-6 days after inoculation.After 3 weeks,the transplanted tumor reached the target volume.The particles implanted in the transplanted tumor are all in rihgt place.?2?the weight of the tumor was weighed.The weight of the tumor in the 0.6 m Ci group and the 0.8 m Ci group was much smaller than that in the control group?P<0.05?.There was no significant difference in the weight between the 0 m Ci group and the control group.The significance?P>0.05?,the difference between the 0.6 m Ci group and the 0.8 m Ci group was not statistically significant?P>0.05?.?3?HE staining pathological sections showed that more degenerative necrotic cells were observed in the transplanted tumor tissues of 0.6 m Ci group and 0.8 m Ci group.The transplanted tumor cells in the control group and 0 m Ci group were closely arranged,with large and dark nuclei and obvious atypia.There was no significant difference between the two groups.?4?Using the TUENL assay,the apoptotic index of the transplanted tumors in the 0.6 m Ci group and the 0.8 m Ci group was higher than that in the control group,the difference was statistically significant?P<0.05?;0.8 m Ci group and 0.6 m Ci group,control group and 0 There was no significant difference in apoptotic index between the m Ci group?P>0.05?.?5?Using immunohistochemical SP method,the expression of Ki-67 was decreased in 0.6 m Ci group and 0.8 m Ci group,and the proliferation index of transplanted tumor was decreased.The difference was statistically significant?P<0.05?.There was no significant difference in Ki-67 expression and proliferation index between 0 m Ci group and control group,0.6 m Ci group and 0.8 m Ci group?both P>0.05?.The positive expression rate of PDCD4 protein was significantly higher in the 0.6 m Ci group than in the control group?P<0.05?.There was no significant difference between the 0.6 m Ci group and the 0.8 m Ci group?P>0.05?;0 m Ci group and the control group There was no statistical significance?P>0.05?.The positive expression rate of P62 protein was lower in the 0.6 m Ci group and 0.8 m Ci group than in the control group?P<0.05?.There was no significant difference between the 0.6 m Ci group and the 0.8 m Ci group?P>0.05?;0 m Ci group There was no statistical significance between the control group and the control group?P>0.05?.?6?Correlation between PDCD4 and PTEN protein,Beclin1 and P62 protein expression in nude mouse tumor tissues: PDCD4 was positively correlated with PTEN?correlation coefficient=0.265,P=0.004<0.05?;Beclin1 was negatively correlated with P62?correlation?Coefficient =-0.312,P = 0.001 < 0.05).Conclusion:Radioactive I¹²⁵ particle implantation significantly inhibited the growth of lung adenocarcinoma xenografts in nude mice.I¹²⁵ particle implantation can inhibit the proliferation of transplanted tumor cells and promote cell apoptosis.After implantation of I¹²⁵ seeds,it may play an anti-tumor role by up-regulating PDCD4 and PTEN,and possibly by up-regulating Beclin1 and down-regulating P62.