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将融合蛋白hVEGF121-M2-X_(10)-βhCG-CTP37作为免疫原,并分别联合化学药物环磷酰胺(CTX)和多西他赛(DTX),探索其对C57BL/6J小鼠B16F10黑色素瘤的抑制效应。将h VEGF121/βhCG融合蛋白(VC)分别与CTX和DTX联合给药(VCC、VCD),免疫接种B16F10黑色素瘤小鼠,对免疫小鼠皮内肿瘤组织周围毛细血管进行计数、测量各组小鼠瘤块体积和重量、对肿瘤组织进行切片分析、检测免疫小鼠脏器指数、MTT法检测脾细胞增殖、LDH法检测特异性杀伤活性。皮内肿瘤组织周围血管计数结果显示,与NS组比,DTX组、VC组以及VCD组均能高效抑制黑色素瘤血管生成(P<0.01);皮下肿瘤抑制结果显示,与NS组相比,DTX组和VCD组抑瘤效果最为显著,抑瘤率分别为60.0%,70.0%,其中VCD组抗肿瘤效果优于VC组或DTX组给药组(P<0.01);肿瘤组织病理学切片结果显示,VCD组的病变程度和炎细胞浸润程度最显著;对小鼠脾脏指数分析结果显示,与NS组相比,DTX组和VCD组的脾脏指数均显著增高(P<0.05);抗肿瘤免疫实验中:与NS组相比,VCD组提高了脾细胞增殖能力和细胞毒作用(P<0.05),且VCD组小鼠的脾细胞杀伤率在效靶比为20∶1、40∶1和80∶1时均具有显著性差异(P<0.05)。h VEGF121/βhCG融合蛋白与化学药物DTX初步表现出协同抗肿瘤的效果,而与化学药物CTX未表现出协同抗肿瘤作用。
The fusion protein hVEGF121-M2-X_ (10) -βhCG-CTP37 was used as immunogen and combined with CTX and docetaxel (docetaxel, respectively) to explore the effect on the B16F10 melanoma Inhibitory effect. The hVEGF121 / βhCG fusion protein (VC) was administered in combination with CTX and DTX respectively (VCC, VCD), and the B16F10 melanoma mice were immunized with the immunized mice to measure the capillaries around the intradermal tumor. The size and weight of the tumor were used to analyze the tumor tissue. The organ index of the mice was measured. The proliferation of spleen cells was detected by MTT assay. The specific killing activity was detected by LDH assay. The intracranial tumor peripheral vascular count results showed that compared with the NS group, DTX group, VC group and VCD group were able to inhibit the angiogenesis of melanoma effectively (P <0.01). The subcutaneous tumor inhibition results showed that compared with NS group, DTX The anti-tumor effect of group VCD and VCD was the most significant, with tumor inhibition rates of 60.0% and 70.0%, respectively. The anti-tumor effect of VCD group was better than that of VC group or DTX group (P <0.01) , The degree of lesion and infiltration of inflammatory cells were the most significant in VCD group. The index of spleen of mice showed that spleen index of DTX group and VCD group were significantly higher than that of NS group (P <0.05); anti-tumor immunity experiment : Compared with the NS group, the VCD group increased the splenocyte proliferation ability and cytotoxicity (P <0.05), and the killing rate of the spleen cells of the VCD group mice was 20: 1, 40: 1 and 80 : 1, there was a significant difference (P <0.05). h The VEGF121 / βhCG fusion protein and the chemotherapeutic drug DTX initially showed a synergistic antitumor effect, but showed no synergistic anti-tumor effect with the chemotherapeutic drug CTX.