CAJ | 학술논문

目的观察18F-氟代脱氧葡萄糖(18F-FDG)内照射对Lewis肺癌移植瘤P53、XIAP与GADD45蛋白表达的影响,探讨其作为内照射治疗药的可行性.方法建立Lewis肺癌C57BL/6小鼠皮下移植瘤模型48只,随机数字表法分为高剂量组、低剂量组和对照组,每组16只.接种后第7天,3组小鼠分别腹腔注射0.2 ml 18F-FDG及等体积生理盐水,使高、低剂量组18F-FDG注射量分别为18.5×107和9.25×107 Bq.第22天处死小鼠,SP免疫组织化学法检测移植瘤组织P53、XIAP与GADD45蛋白表达.结果每种蛋白3组小鼠间表达差异有统计学意义(x2=8.30、16.02、7.68,P ＜0.05).3组小鼠Lewis肺癌P53蛋白表达的平均积分光密度分别从对照组的(0.089±0.033)随照射剂量增大为高剂量组的(0.315±0.028);XIAP蛋白表达的平均积分光密度从(0.422±0.034)逐步减小为(0.149±0.055);GADD45蛋白表达的平均积分光密度从(0.126±0.023)逐步上升为(0.383±0.035).3组间蛋白表达量差异有统计学意义(P53:F =5.26,P＜0.05;XIAP:F=4.29,P＜0.05;GADD45:F=5.98,P＜0.05).结论 18F-FDG能够上调P53和GADD45蛋白表达,下调XIAP蛋白表达,促使小鼠Lewis肺癌组织细胞以P53依赖的方式凋亡,抑制Lewis肺癌移植瘤生长.
목적 관찰18F-불대탈양포도당(18F-FDG)내조사대Lewis폐암이식류P53、XIAP여GADD45단백표체적영향,탐토기작위내조사치료약적가행성.방법 건립Lewis폐암C57BL/6소서피하이식류모형48지,수궤수자표법분위고제량조、저제량조화대조조,매조16지.접충후제7천,3조소서분별복강주사0.2 ml 18F-FDG급등체적생리염수,사고、저제량조18F-FDG주사량분별위18.5×107화9.25×107 Bq.제22천처사소서,SP면역조직화학법검측이식류조직P53、XIAP여GADD45단백표체.결과 매충단백3조소서간표체차이유통계학의의(x2=8.30、16.02、7.68,P ＜0.05).3조소서Lewis폐암P53단백표체적평균적분광밀도분별종대조조적(0.089±0.033)수조사제량증대위고제량조적(0.315±0.028);XIAP단백표체적평균적분광밀도종(0.422±0.034)축보감소위(0.149±0.055);GADD45단백표체적평균적분광밀도종(0.126±0.023)축보상승위(0.383±0.035).3조간단백표체량차이유통계학의의(P53:F =5.26,P＜0.05;XIAP:F=4.29,P＜0.05;GADD45:F=5.98,P＜0.05).결론 18F-FDG능구상조P53화GADD45단백표체,하조XIAP단백표체,촉사소서Lewis폐암조직세포이P53의뢰적방식조망,억제Lewis폐암이식류생장.
Objective To study the effects of internal exposure of 18F-FDG (18F-2-deoxy-2-fiuoroD-glucose) on the protein expressions of P53,XIAP (X-linked inhibitors of apoptosis protein) and GADD (growth arrest and DNA damage)45 in Lewis lung carcinoma,and to explore the possibility of applying 18F-FDG as a radiotherapy drug in vivo.Methods Lewis lung cancer transplanted tumor models were established via subcutaneous injection of 0.2 ml of 2 × 107/ml Lewis lung carcinoma cells at left hind limbs of 48 C57BL/6 mice that were randomly divided into high dose group,low dose group and control group with 16 mice each.After 7 d of cancer cell inoculation,18.5 × 107 Bq and 9.25 × 107 Bq of 18F-FDG in 0.2 ml saline or equal volume of physiological saline was intraperitoneally injected into three group mice,respectively.22 d post inoculation,the protein expressions of P53,XIAP and GADD45 were immuohistochemically detected by using SP approach.Results There was significant difference among the protein expressions in each group (x2 =8.30,16.02,7.68,P ＜0.05).The mean integral optic density of protein expression increased from 0.089 ± 0.033 in control group to 0.315 ± 0.028 in high dose group for P53,and from 0.126 ± 0.023 to 0.383 ±-0.035 for GADD45,but it decreased from 0.422 ± 0.034 to 0.149 ± 0.055 for XIAP.There was significantly difference of these protein expressions in each group (P53:F=5.26,P＜0.05;XIAP:F=4.29,P ＜0.05;GADD45:F=5.98,P ＜0.05).Conclusions 18F-FDG can up-regulate the expressions of P53 and GADD45 proteins and down-regulate the expression of XIAP protein in tumor cells,and it inhibits tumor growth by promoting cell apoptosis in the Lewis lung carcinoma tissue with a P53-dependent manner.