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目的研究IL-24基因联合顺铂对宫颈癌裸鼠移植瘤的生长抑制作用以及对肿瘤细胞侵袭能力的影响。方法构建宫颈癌Siha细胞裸鼠肿瘤模型;根据治疗方案将动物模型分为6组:PBS组、pDC316空质粒组、IL-24组(pDC316-hIL-24质粒)、半量顺铂(2.5 mg/kg)组、全量顺铂(5 mg/kg)组和联合组(pDC316-hIL-24质粒联合半量顺铂)。实验中,通过比较各组移植瘤体积和动物体重变化,评价IL-24基因联合顺铂的抑瘤效果和药物不良反应。应用PCR法检测移植瘤中IL-24的表达,Western blot法检测各组移植瘤中β-catenin和E-cadherin的表达水平。结果重组质粒pDC316-hIL-24成功转染移植瘤细胞并表达;联合组治疗后移植瘤体积(613.1±44.5)mm3,与全量顺铂组治疗后肿瘤体积(281.4±114.9)mm3比较,差别无统计学意义(P>0.05);联合组下调β-catenin(β-catenin/β-actin为0.55±0.02)和上调E-cadherin(E-cadherin/β-actin为1.37±0.17)的表达效果最明显。结论 IL-24基因联合半量顺铂治疗能达到全量顺铂的抑瘤效果,减少化疗药物的使用剂量;IL-24基因可通过下调β-catenin和上调E-cadherin的表达水平进而抑制Siha肿瘤细胞侵袭能力;联合治疗比单独使用IL-24或顺铂能更大程度地抑制Siha细胞的侵袭力。
Objective To study the effects of IL-24 gene combined with cisplatin on the growth of cervical cancer xenografts in nude mice and its effect on tumor cell invasion. Methods The tumor model of cervical cancer Siha cells was established. According to the treatment protocol, the animal models were divided into 6 groups: PBS group, pDC316 empty plasmid group, IL-24 group (pDC316-hIL-24 plasmid), cisplatin (2.5 mg / kg) group, the total amount of cisplatin (5 mg / kg) group and the combination group (pDC316-hIL-24 plasmid combined with semi-dose of cisplatin). In the experiment, the antitumor effect and adverse drug reactions of IL-24 gene combined with cisplatin were evaluated by comparing the volume of tumor xenograft in each group and the change of body weight. The expression of IL-24 in the transplanted tumor was detected by PCR, and the expression of β-catenin and E-cadherin in the transplanted tumors were detected by Western blot. Results The recombinant plasmid pDC316-hIL-24 was successfully transfected into tumor cells and the tumor volume was (613.1 ± 44.5) mm3 in the combined group, which was significantly lower than that of the full-thickness cisplatin group (281.4 ± 114.9) mm3 (P> 0.05). The combined effect of down-regulation of β-catenin (0.55 ± 0.02) and up-regulation of E-cadherin (1.37 ± 0.17) obvious. Conclusion IL-24 gene combined with cisplatin can inhibit the tumor growth of cisplatin and reduce the dose of chemotherapeutic drugs. IL-24 gene can inhibit the expression of E-cadherin and down-regulate the expression of E-cadherin Invasive ability; Combination therapy can inhibit Siha cell invasiveness to a greater extent than IL-24 or cisplatin alone.