损伤调节自噬调控基因对胃癌SGC7901细胞裸鼠移植瘤放射敏感性的影响

Effects of damage-regulated autophagy modulator on the radiosensitivity of SGC7901 cell xenografts in nude mice

目的研究损伤调节自噬调控基因（DRAM）对胃癌SGC7901细胞移植瘤放射敏感性的影响。方法取对数生长期的人胃癌SGC7901细胞建立裸鼠皮下移植瘤模型．随机分为空白对照组、DRAM组（在瘤体约为1．0cm^3时．在瘤周注射携带DRAM基因的腺病毒Admax-pDC315．DRAM—EGFP）、放疗组、放疗联合DRAM组。对瘤体进行剂量为10Gy局部放疗．分别在放疗后3、6、9d处死裸鼠，切取肿瘤，计算抑瘤率。用免疫组化方法检测P53、PCNA、C-myc、Fas—L蛋白的表达。结果放疗联合DRAM组的抑瘤率在3、6、9d分别为9．3％、14．1％、16．7％，均显著高于单纯放疗组（5．0％、8．8％、6．5％）（P〈0．05）；在空白对照组、DRAM组、放疗组、放疗联合DRAM组中．随时间延长PCNA和C-myc蛋白表达的阳性率逐渐下降．而P53和Fas—L蛋白表达的阳性率逐渐增强。结论DRAM基因可通过促进细胞凋亡和抑制细胞增殖．增强裸鼠皮下胃癌移植瘤的放射敏感性。

Objective To investigate the effects of damage-regulated autophagy modulator （DRAM） on radiosensitivity and the related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice. Methods Nude mice were randomly divided into model control group, radiotherapy group, and DRAM treatment group and radiotherapy combined with DRAM treatment group. When volume of transplantation tumor were 1.0 cm^3, radiotherapy, DRAM treatment was given. On days 3, 6 and 9 after treatment, the inhibition rate of tumor growth, pathological changes in tumor specimens, expression levels of P53, proliferating cell nuclear antigen（PCNA）, C-myc, Fas-L, as well as apoptosis indexes in tumor samples were observed. Results Inhibition rates of tumor in DRAM combined with radiotherapy were 9.3% ,14.1% ,16.7% on day 3, 6 and 9, respectively, all significantly higher than those in the radiotherapy group （5.0%, 8.8%,6.5%,P〈0.05）. The expressions of PCNA and C-mye protein were down-regulated, while the expressions of P53 and Fas-L were upregulated. Conclusion Damage-regulated autophagy modulator gene may promote cell apoptosis and inhibit cell growth to enhance the radiosensitivity of transplantated gastric tumor in vivo in nude mice.