ABSTRACT
AIM:To explore whether there is synergistic effect of recombinant human endostatin ( rh-Endo ) and paclitaxel (Pac) in the time window of vascular normalization and the role of magnetic resonance imaging (MRI) in early assessment of chemotherapy by observing the response of human triple -negative breast cancer ( TNBC) to Pac after vascular normalization in nude mice .METHODS:The human TNBC MDA-MB-231 cells were planted in the subcutaneous region of right lower abdomen of BALB/c-nu female nude mice .These nude mice were randomly divided into 4 groups (n=7).rh-Endo was given for 17 consecutive days in rh-Endo group and rh-Endo+Pac group.Pac was given on the 6th and 12th days in Pac group and rh-Endo+Pac group.The dosage of both drugs was 10 mg· kg-1· d-1(ip).On the day before the treatment and the 5th, 11th and 17th days after treatment, all the transplanted tumors were examined by MRI . All the mice were killed by cervical dislocation and their transplanted tumors were taken down for examinations after the last MRI on the 17th day.The changes of pathology, immunohistochemisty, microvessel density (MVD) and Ki67 expression were measured.RESULTS:On the 17th day, the volume of transplanted tumor in rh-Endo+Pac group was smaller than that in model group and rh-Endo group ( P<0.05 ) , and no difference between rh-Endo+Pac group and Pac group was found.On the 17th day, the tumor inhibitory rates in rh-Endo group, Pac group and rh-Endo+Pac group were 14.61%, 39.08%and 54.79%, respectively.The slow diffusion coefficient in Pac group was increased compared with model group , while it was decreased compared with rh-Endo+Pac group (P<0.05).No distant metastatic lesion in the tumor-bearing mice was observed .The necrotic rates in rh-Endo+Pac group and Pac group were higher than those in model group and rh-Endo group.The MVD in model group was higher than that in the other 3 groups.The MVD in rh-Endo+Pac group was decreased compared with Pac group and rh-Endo group .The Ki67 level in rh-Endo+Pac group was decreased compared with rh-Endo group , and no difference between rh-Endo+Pac group and Pac group was detected .CONCLUSION:In the time window of vascular normalization , the combination of Pac and rh-Endo has a significant antitumor effect on TNBC , but this study did not observe a significant synergistic effect of the 2 drugs.The change of slow diffusion coefficient can predict the therapeutic effect in advance .
ABSTRACT
AIM:To explore whether there is synergistic effect of recombinant human endostatin ( rh-Endo ) and paclitaxel (Pac) in the time window of vascular normalization and the role of magnetic resonance imaging (MRI) in early assessment of chemotherapy by observing the response of human triple -negative breast cancer ( TNBC) to Pac after vascular normalization in nude mice .METHODS:The human TNBC MDA-MB-231 cells were planted in the subcutaneous region of right lower abdomen of BALB/c-nu female nude mice .These nude mice were randomly divided into 4 groups (n=7).rh-Endo was given for 17 consecutive days in rh-Endo group and rh-Endo+Pac group.Pac was given on the 6th and 12th days in Pac group and rh-Endo+Pac group.The dosage of both drugs was 10 mg· kg-1· d-1(ip).On the day before the treatment and the 5th, 11th and 17th days after treatment, all the transplanted tumors were examined by MRI . All the mice were killed by cervical dislocation and their transplanted tumors were taken down for examinations after the last MRI on the 17th day.The changes of pathology, immunohistochemisty, microvessel density (MVD) and Ki67 expression were measured.RESULTS:On the 17th day, the volume of transplanted tumor in rh-Endo+Pac group was smaller than that in model group and rh-Endo group ( P<0.05 ) , and no difference between rh-Endo+Pac group and Pac group was found.On the 17th day, the tumor inhibitory rates in rh-Endo group, Pac group and rh-Endo+Pac group were 14.61%, 39.08%and 54.79%, respectively.The slow diffusion coefficient in Pac group was increased compared with model group , while it was decreased compared with rh-Endo+Pac group (P<0.05).No distant metastatic lesion in the tumor-bearing mice was observed .The necrotic rates in rh-Endo+Pac group and Pac group were higher than those in model group and rh-Endo group.The MVD in model group was higher than that in the other 3 groups.The MVD in rh-Endo+Pac group was decreased compared with Pac group and rh-Endo group .The Ki67 level in rh-Endo+Pac group was decreased compared with rh-Endo group , and no difference between rh-Endo+Pac group and Pac group was detected .CONCLUSION:In the time window of vascular normalization , the combination of Pac and rh-Endo has a significant antitumor effect on TNBC , but this study did not observe a significant synergistic effect of the 2 drugs.The change of slow diffusion coefficient can predict the therapeutic effect in advance .