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目的研究携带基质金属蛋白酶组织抑制因子-3(TIMP-3)的重组腺病毒(Ad-TIMP-3)对人乳头瘤病毒(HPV)阳性子宫颈癌细胞放疗敏感性的影响。方法采用Ad-TIMP-3感染HeLa-Luc和CaSki细胞,MTT法检测Ad-TIMP-3对HeLa-Luc和CaSki细胞增殖的影响,平板克隆形成实验检测Ad-TIMP-3与X线联合应用对细胞生长能力的影响。将经过不同处理的HeLa-Luc细胞接种于裸鼠腋下,分别观察正常对照组、单独病毒组、单独放射组和联合应用组裸鼠体内肿瘤的生长情况,绘制生长曲线。结果 Ad-TIMP-3能显著抑制HeLa-Luc和CaSki细胞增殖,呈现剂量效应关系。Ad-TIMP-3与X线联合应用可显著减少HeLa-Luc和CaSki细胞平板克隆形成数(P均<0.05)。单独病毒组、单独放射组和联合应用组裸鼠移植瘤重量分别为(0.216±0.098)、(0.276±0.073)和(0.044±0.043)g,均明显低于正常对照组的(0.534±0.218)g(P均<0.05),联合应用组明显低于单独病毒组和单独放射组(P均<0.05)。单独病毒组、单独放射组和联合应用组的抑瘤率分别为59.60%、48.30%和91.80%。结论 Ad-TIMP-3能抑制子宫颈癌细胞增殖,与X线联合应用可显著提高子宫颈癌细胞对放射治疗的敏感性,抑制子宫颈癌细胞体内致瘤能力。
Objective To investigate the effect of recombinant adenovirus carrying TIMP-3 (TIMP-3) on the radiosensitivity of human papillomavirus (HPV) -positive cervical cancer cells. Methods HeLa-Luc and CaSki cells were infected with Ad-TIMP-3. The proliferation of HeLa-Luc and CaSki cells was detected by MTT assay. The combination of Ad-TIMP-3 and X-ray Effect of cell growth ability. The differently treated HeLa-Luc cells were inoculated into the armpit of nude mice to observe the growth of tumors in normal control group, single virus group, radiotherapy alone group and combination group, and the growth curve was drawn. Results Ad-TIMP-3 significantly inhibited the proliferation of HeLa-Luc and CaSki cells, showing a dose-response relationship. The combination of Ad-TIMP-3 and X-ray can significantly reduce the number of plate clone formation in HeLa-Luc and CaSki cells (all P <0.05). The tumor weights of nude mice in single virus group, radiation alone group and combination group were (0.216 ± 0.098), (0.276 ± 0.073) and (0.044 ± 0.043) g, respectively, which were significantly lower than those in normal control group (0.534 ± 0.218) g respectively (all P <0.05). The combined application group was significantly lower than that of single virus group and single radiotherapy group (all P <0.05). The inhibition rates of single virus group, radiotherapy alone group and combination group were 59.60%, 48.30% and 91.80%, respectively. Conclusions Ad-TIMP-3 can inhibit the proliferation of cervical cancer cells. Combined with X-ray, Ad-TIMP-3 can significantly enhance the sensitivity of cervical cancer cells to radiotherapy and inhibit the tumorigenicity of cervical cancer cells in vivo.