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激光联合环磷酰胺对小鼠肿瘤增殖及血管新生的影响

Effects of laser combined with Cyclophosphamide on tumor growth and angiogenesis of hepatocellular carcinoma in mice
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摘要 目的探讨低能量激光联合环磷酰胺(CTX)对小鼠肿瘤增殖及血管新生的影响。方法建立荷瘤小鼠模型,随机将40只荷瘤小鼠分为生理盐水对照组(NS组)、低能量激光照射组(JG组)、环磷酰胺组(CTX组)、低能量激光联合环磷酰胺组(JG+CTX组),每组各10只。分别给予相应药物或激光治疗连续10 d。观察肿瘤生长情况,测量荷瘤小鼠的瘤质量、脾质量,计算抑瘤率及脾指数;原位杂交法检测瘤组织血管内皮生长因子(VEGF)mRNA表达,免疫组化方法检测瘤组织微血管密度(microvessel density,MVD)及增殖细胞核抗原(PCNA)的表达情况。结果①NS组小鼠给药第7、10天体重[(23.24±0.60)、(26.79±0.59)g]低于JG组[(26.74±1.23)、(26.79±0.59)g]、CTX组[(25.55±0.71)、(25.69±0.35)g]、JG+CTX组[(26.09±0.68)、(26.41±0.67)g],差异均有高度统计学意义(均P<0.01);JG组、CTX组和JG+CTX组抑瘤率分别为(50.82±0.33)%、(65.57±0.24)%、(53.69±0.33)%;JG组、JG+CTX组的瘤质量[(1.20±0.43)、(1.13±0.43)g]低于NS组[(2.44±0.23)g],JG组、JG+CTX组的脾指数[(14.30±0.20)、(14.51±0.16)‰]高于NS组[(9.96±0.18)‰],差异均有统计学意义(P<0.05或P<0.01)。②JG组、CTX组、JG+CTX组VEGF mRNA平均灰度[(62.28±2.36)、(68.12±2.60)、(69.95±4.38)]低于NS组(49.87±3.76),差异有高度统计学意义(P<0.01);JG组VEGF mRNA平均灰度低于与JG+CTX组,差异有高度统计学意义(P<0.01);JG+CTX组VEGF mRNA平均灰度与CTX组比较,差异无统计学意义(P=0.234)。NS组MVD值(14.57±0.58)高于JG组(13.52±0.33)、CTX组(12.30±0.29)、JG+CTX组(11.49±0.44),差异有高度统计学意义(P<0.01);JG+CTX组MVD值低于JG组、CTX组,差异有高度统计学意义(P<0.01)。③NS组PCNA阳性细胞数[(80.6±2.01)个]高于JG组[(73.8±2.57)个]、CTX组[(63.7±2.75)个]、JG+CTX组[(66.1±3.38)个],差异有高度统计学意义(P<0.01);CTX组与JG+CTX组PCNA阳性细胞数差异无统计学意义(P>0.05)。结论低能量激光对小鼠移植瘤具有一定的生长抑制作用,联合环磷酰胺可明显抑制肿瘤细胞的增殖及血管生成,具有协同抗肿瘤作用。 Objective To study effects of laser combined with Cyclophosphamide on tumor growth and angiogenesis of hepatocellular carcinoma in mice.Methods Tumor loaded mice models were established,then 40 cases of tumor loaded mouse were divided randomly into NS group,low energy laser irradiation group(JG group),Cyclophosphamide group(CTX group) and low energy laser irradiation combined with Cyclophosphamide group(JG+CTX group) with 10 mouse in each group.The drugs or laser irradiation were given every day in each group for 10 days.Tumor growth sit uation,tumor weight and spleen weight were measured,tumor inhibitory rate and spleen index were calculated.Ex pression of VEGF mRNA was detected by in situ hybridization,the expression of MVD and PCNA were detected by immune histochemistry.Results ① The weight in NS group 7,10 days after the drug administration [(23.24 ±0.60),(26.79±0.59) g] were lower than those in JG group [(26.74 ±1.23),(26.79±0.59) g],CTX group [(25.55±0.71),(25.69± 0.35) g] and JG+CTX group [(26.09±0.68),(26.41±0.67) g],the differences were statistically significant(P 0.01);tumor inhibition rate in JG group,CTX group and JG+CTX group were(50.82 ±0.33)%,(65.57±0.24)%,(53.69±0.33)%;tumor weight in JG group [(1.20±0.43) g] and JG+CTX group [(1.13±0.43) g] were all lower than those in NS group [(2.44±0.23) g],spleen index in JG group [(14.30 ±0.20)‰] and JG+CTX group [(14.51±0.16)‰] were all higher than those in NS group [(9.96±0.18)‰],the differences were statistically significant(P 0.01 or P 0.05).②Average grey degree of VEGF mRNA in JG group(62.28±2.36),CTX group(68.12±2.60) and JG+CTX group(69.95±4.38) were all lower than those in NS group(49.87±3.76),the differences were statistically significant(P 0.01);average grey degree of VEGF mRNA in JG group was lower than that in JG+CTX group,the difference was statistically significant(P 0.01);the difference of average grey degree of VEGF mRNA in JG+CTX group and CTX group was not statistically significant(P = 0.234).MVD value in NS group(14.57± 0.58) were higher than those in JG group(13.52±0.33),CTX group(12.30±0.29) and JG+CTX group(11.49±0.44),the differences were statistically significant(P 0.01);MVD value in JG+CTX group were lower than those in JG group and CTX group,the differences were statistically significant(P 0.01).③PCNA Positive cell number in NS group [(80.6±2.01) numbers] were higher than those in JG group [(73.8±2.57) numbers],CTX group [(63.7±2.75) numbers],JG+CTX group [(66.1±3.38) numbers],the differences were statistically significant(P 0.01);the difference of PCNA Positive cell number in CTX group and JG+CTX group were not statistically significant(P 0.05).Conclusion Low energy laser irradiation combined with Cyclophosphamide can obviously inhibit the proliferation of tumor cells and angiogenesis,which show synergistic antitumor effect.
出处 《中国医药导报》 CAS 2013年第15期34-36,39,共4页 China Medical Herald
基金 内蒙古自治区自然科学基金项目(编号2012MS1181)
关键词 肝癌 低能量激光 环磷酰胺 血管新生 增殖细胞核抗原 Hepatocellular carcinoma Low energy laser Cyclophosphamide Angiogenesis Proliferating cell nuclear antigen
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