摘要
目的观察肿瘤坏死因子-α(TNF-α)和组织金属蛋白酶抑制物(TIMP-1)联合作用对肝癌裸鼠移植瘤生长的影响。方法利用体外培养的人肝癌HepG2细胞,移植到裸鼠背脊部皮下后,在TNF-α单独作用以及TNF-α和TIMP-1同时作用的条件下,检测其对肝癌移植瘤生长的抑制作用,逆转录聚合酶链反应(RT-PCR)检测肿瘤组织中增殖细胞核抗原(PCNA)、凋亡抑制基因Bcl-2mRNA表达,westernblot免疫印迹检测肿瘤组织中基质金属蛋白酶-9(MMP-9)的蛋白含量。结果治疗后24天T/C比值(TNF-α+TIMP-1组:对照组)为42.6%,治疗结束后1周为36.4%,TNF-α+TIMP-1组瘤重明显轻于对照组和TNF-α组,差异有显著性意义(P<0.05),对照组与TNF-α组相比较,瘤重无明显变化(P>0.05);TNF-α和TIMP-1联合作用后,肿瘤组织中PCNA和Bcl-2mRNA含量明显少于对照组(P<0.01),但TNF-α单独作用后无明显变化(P>0.05);TNF-α单独作用后,肿瘤组织中MMP-9蛋白含量多于对照组(P<0.05),联合作用后明显抑制了MMP-9的产生,血管生成作用明显减弱。结论 TNF-α联合TIMP-1明显抑制肝癌裸鼠移植瘤的生长、血管生成及侵袭转移,促进肿瘤细胞的凋亡,明显提高了TNF-α的抗肿瘤效果。
Objective To investigate the inhibitive effect of tumor necrosis factor-a （TNF-a）and tis- sue inhibit metalloproteinase-l（TIMP-1） on the growth of hepatocellular carcinoma xenografted in nude mice. Method The cultured hepatoma HepG2 cell in vitro was subcutaneously injected into Balb/c nude mice to detect the inhibition of TNF-α associated with TIMP-1 or TNF-α solely on the growth of hepatocel-kdar carcinoma xenografted in nude mice. The expression of PCNA and Bcl-1 mRNA in tumor tissues was analyzed with RT-PCR, and the expression of MMP-9 protein in tumor tissue was analyzed by Western- blot. Results T/C ratio （TNF-α and TIMP-1 group ： control group） is 42.6% in 24 days after treatment, and it is 36.4% in 7 days after treatment. In the meantime, the weight of tumor in TNF-α and TIMP-1 group isobviously lighter than the other two groups（P〈0.05）, there is no obvious difference between TNF-α group and control group （P〉0.05）; the PCNA and Bcl-2 mRNA expression level of tumor tissue in TNF-α and TIMP-1 group is obviously less than that of the control group （P〈0.05）, there is no significant difference after treatmentwith TNF-a solely （P〉0.05）; the protein MMP-9 expression of tumor tissue after treatment with TNF-αsolely is stronger than control group, the combined eatment of TNF-α and TIMP-1 obviously inhibit the produc-tion of MMP-9, and the angiogenesis obviously decreased. Conclusion Combination treatment can sig- nificantly inhibit the growth, angiogenesis and metastasis of hepatocellular carcinoma xenografted in nude mice. It obviously promotes TNF-α to induce the apoptosis of transplanted tumor cells.
出处
《肿瘤药学》
CAS
2011年第3期189-192,共4页
Anti-Tumor Pharmacy
关键词
TNF-Α
TIMP-1
肝癌
裸鼠
移植瘤
TNF-α
TIMP-1
Hepatocellular Carcinoma
Nude Mice
Xenografted Tumor
