中国肿瘤临床
中國腫瘤臨床
중국종류림상
CHINESE JOURNAL OF CLINICAL ONCOLOGY
2010年
4期
194-197
,共4页
王士勇%张远%杨云锋%杜微丽%张晖%刘飒%张哲%何英%王佳玲%武秀艳
王士勇%張遠%楊雲鋒%杜微麗%張暉%劉颯%張哲%何英%王佳玲%武秀豔
왕사용%장원%양운봉%두미려%장휘%류삽%장철%하영%왕가령%무수염
髓样抑制细胞%亚砷酸%肝细胞癌%小鼠
髓樣抑製細胞%亞砷痠%肝細胞癌%小鼠
수양억제세포%아신산%간세포암%소서
Myeloid derived suppressor cells%Arsenious acid%Hepatocellular carcinoma%Mice
目的:探讨髓样抑制细胞(MDSCs)与肿瘤发生、发展的相关性,寻找抑制肿瘤生长的方法.方法:建立H_(22)肝癌细胞昆明鼠皮下移植瘤模型.用共聚焦显微镜观察MDSCs形态;应用流式细胞仪检测外周血及脾脏中MDSCs数量在肿瘤生长过程中的变化趋势;给予As_2O_3药物干预,即随机分为对照组、As_2O_3低剂量组(2mg/kg)、As_2O_3高剂量组(4mg/kg);每周腹腔给药2次,重复上述测量,统计学分析组间差异;体外细胞培养观察As_2O_3对小鼠MDSCs数量的直接影响.结果:皮下接种肿瘤细胞株后,瘤重逐渐增加,第25天增加至5.67g,外周血和脾脏MDSCs比例也逐渐增加,分别达20.46%和9.50%;对瘤重与外周血和脾脏MDSCs比例的变化趋势进行相关性分析,相关系数r值分别为0.95和0.96(t=-5.270、5.939,P<0.05),两者明显呈正相关关系.当用As_2O_3药物干预时,外周血低剂量组和高剂量组MDSCs比例在第28天上升至11.31%和10.00%,明显低于阴性对照组(t=3.193、5.486,P<0.05),且高剂量组MDSCs比例明显低于低剂量组(t=3.066,P<0.05);脾脏低剂量组和高剂量组MDSCs比例在第28天上升至10.90%和9.04%,明显低于阴性对照组(t=3.586、5.279,P<0.05),但高、低剂量组间差异无统计学意义(t=1.298,P>0.05).体外实验中.在加入H_(22)肿瘤腹水上清后.培养液中MDSCs比例于第12天上升至12.67%;加入As_2O_3继续培养,MDSCs的比例于第18天下降至7.44%,分别与其前一时间点比较,差异有统计学意义(P<0.05).结论:荷H_(22)肝癌细胞小鼠体内MDSCs比例随着肿瘤负荷增大而增加,两者存在正相关性;As_2O_3可以降低MDSCs的比例,缓解肿瘤发生、发展.
目的:探討髓樣抑製細胞(MDSCs)與腫瘤髮生、髮展的相關性,尋找抑製腫瘤生長的方法.方法:建立H_(22)肝癌細胞昆明鼠皮下移植瘤模型.用共聚焦顯微鏡觀察MDSCs形態;應用流式細胞儀檢測外週血及脾髒中MDSCs數量在腫瘤生長過程中的變化趨勢;給予As_2O_3藥物榦預,即隨機分為對照組、As_2O_3低劑量組(2mg/kg)、As_2O_3高劑量組(4mg/kg);每週腹腔給藥2次,重複上述測量,統計學分析組間差異;體外細胞培養觀察As_2O_3對小鼠MDSCs數量的直接影響.結果:皮下接種腫瘤細胞株後,瘤重逐漸增加,第25天增加至5.67g,外週血和脾髒MDSCs比例也逐漸增加,分彆達20.46%和9.50%;對瘤重與外週血和脾髒MDSCs比例的變化趨勢進行相關性分析,相關繫數r值分彆為0.95和0.96(t=-5.270、5.939,P<0.05),兩者明顯呈正相關關繫.噹用As_2O_3藥物榦預時,外週血低劑量組和高劑量組MDSCs比例在第28天上升至11.31%和10.00%,明顯低于陰性對照組(t=3.193、5.486,P<0.05),且高劑量組MDSCs比例明顯低于低劑量組(t=3.066,P<0.05);脾髒低劑量組和高劑量組MDSCs比例在第28天上升至10.90%和9.04%,明顯低于陰性對照組(t=3.586、5.279,P<0.05),但高、低劑量組間差異無統計學意義(t=1.298,P>0.05).體外實驗中.在加入H_(22)腫瘤腹水上清後.培養液中MDSCs比例于第12天上升至12.67%;加入As_2O_3繼續培養,MDSCs的比例于第18天下降至7.44%,分彆與其前一時間點比較,差異有統計學意義(P<0.05).結論:荷H_(22)肝癌細胞小鼠體內MDSCs比例隨著腫瘤負荷增大而增加,兩者存在正相關性;As_2O_3可以降低MDSCs的比例,緩解腫瘤髮生、髮展.
목적:탐토수양억제세포(MDSCs)여종류발생、발전적상관성,심조억제종류생장적방법.방법:건립H_(22)간암세포곤명서피하이식류모형.용공취초현미경관찰MDSCs형태;응용류식세포의검측외주혈급비장중MDSCs수량재종류생장과정중적변화추세;급여As_2O_3약물간예,즉수궤분위대조조、As_2O_3저제량조(2mg/kg)、As_2O_3고제량조(4mg/kg);매주복강급약2차,중복상술측량,통계학분석조간차이;체외세포배양관찰As_2O_3대소서MDSCs수량적직접영향.결과:피하접충종류세포주후,류중축점증가,제25천증가지5.67g,외주혈화비장MDSCs비례야축점증가,분별체20.46%화9.50%;대류중여외주혈화비장MDSCs비례적변화추세진행상관성분석,상관계수r치분별위0.95화0.96(t=-5.270、5.939,P<0.05),량자명현정정상관관계.당용As_2O_3약물간예시,외주혈저제량조화고제량조MDSCs비례재제28천상승지11.31%화10.00%,명현저우음성대조조(t=3.193、5.486,P<0.05),차고제량조MDSCs비례명현저우저제량조(t=3.066,P<0.05);비장저제량조화고제량조MDSCs비례재제28천상승지10.90%화9.04%,명현저우음성대조조(t=3.586、5.279,P<0.05),단고、저제량조간차이무통계학의의(t=1.298,P>0.05).체외실험중.재가입H_(22)종류복수상청후.배양액중MDSCs비례우제12천상승지12.67%;가입As_2O_3계속배양,MDSCs적비례우제18천하강지7.44%,분별여기전일시간점비교,차이유통계학의의(P<0.05).결론:하H_(22)간암세포소서체내MDSCs비례수착종류부하증대이증가,량자존재정상관성;As_2O_3가이강저MDSCs적비례,완해종류발생、발전.
Objective: To discuss the correlation between myeloid derived suppressor cells (MDSCs) and hepatic trans-planted tumor and to explore new ways to inhibit the development of hepatic cancer. Methods: We established the animal models with H_(22) hepatic carcinoma cells transplanted to the anterior right limb. Then the MDSCs morphology was observed with confocal microscopy and the proportion of MDSCs in blood and spleen was measured with flow cytometry. The 36 mice were divided into three groups: the control group, the low-dose group (2mg/kg) and the high-dose group (4mg/kg). Then As_2O_3 was injected twice a week to the mice before repeating the aforementioned measures. The direct effects of As_2O_3 on MDSCs cultured with H_(22)-ascites supernatant was observed. Results: At 25 days after transplantion, the tumor weight was increased to 5.67g, and the proportion of MDSCs in blood and spleen was increased to 20.46% and 9.50%, re-spectively. There was a positive correlation between hepatic transplanted tumor and MDSCs in blood and spleen and the relative factors were 0.95 and 0.96, respectively (t=-5.270 and 5.939, P<0.05). With the effect of As_2O_3, the proportion of MD-SCs in blood in low-dose group and high-dose group was 11.31% and 10.00% at 28 days after treatment, lower than that in the control group (t=3.193 and 5.486, P<0.05), and there was also a statistical difference between the high-dose group and low-dose group (t=3.066, P<0.05). The proportion of MDSCs in the spleen in low-dose group and high-dose group was 10.90% and 9.04% at 28 days, lower than that in the control group (t=3.586.and 5.279, P<0.05), but there was no statistical difference between the high-dose group and low-dose group (1=1.298, P>0.05). In vitro, the proportion of MDSCs in nutrient fluid was increased to 12.67% at 12 days after treatment with H_(22)-ascites supematant, and was decreased to 7.44% at 18 days after treatment with As_2O_3. Conclusion: The proportion of MDSCs in H_(22) tumor-bearing mice is increased because of tu-mor development. There is a positive correlation between MDSCs and hepatic transplanted tumor. As_2O_3 can decrease MD-SCs and inhibit tumor growth.
