中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2012年
9期
652-657
,共6页
黄海雯%陈萍%李炳宗%傅晋翔%李军%张晓慧%刘睿%范银银%张宏%Howard C.H.Chow%Anska Y.H.Leung%Raymond Liang
黃海雯%陳萍%李炳宗%傅晉翔%李軍%張曉慧%劉睿%範銀銀%張宏%Howard C.H.Chow%Anska Y.H.Leung%Raymond Liang
황해문%진평%리병종%부진상%리군%장효혜%류예%범은은%장굉%Howard C.H.Chow%Anska Y.H.Leung%Raymond Liang
多发性骨髓瘤%罗格列酮%全反式维甲酸%裸鼠%血管内皮生长因子
多髮性骨髓瘤%囉格列酮%全反式維甲痠%裸鼠%血管內皮生長因子
다발성골수류%라격렬동%전반식유갑산%라서%혈관내피생장인자
Multiple myeloma%Rosiglitazone%All-trans-retinoic acid,ATRA%Nude mice%Vascular endothelial growth factor,VEGF
目的 研究罗格列酮(RGZ)和全反式维甲酸(ATRA)对多发性骨髓瘤裸鼠移植瘤生长和血管形成的影响.方法 分别以不同浓度的RGZ和ATRA或RGZ+ ATRA处理U266细胞24h,采用半定量RT-PCR法检测各组U266细胞中血管内皮细胞生长因子(VEGF)的表达.将U266细胞接种于4周龄Balb/c裸鼠一侧肩胛部皮下,接种1周后分别以RGZ和RGZ+ ATRA腹腔注射干预,连续给药21 d.第21天处死裸鼠,剥离皮下肿瘤并称重,将肿瘤组织分别进行HE和CD34、VEGF免疫组化染色.结果 未经处理的对照组U266细胞中VEGF mRNA高表达；经RGZ处理后,VEGF mRNA的表达水平下调；经RGZ+ ATRA处理后,VEGF mRNA的表达水平较RGZ组更低.U266细胞接种后,在裸鼠皮下均可形成肿瘤.腹腔用药后,RGZ组裸鼠移植瘤的体积和重量分别为(785±262)mm3和(1748±365)mg,均明显低于对照组(均P＜0.01)；RGZ+ ATRA组移植瘤的体积和重量分别为(154±89)mm3和(626±102) mg,均明显低于RGZ组(均P＜0.05).各组裸鼠移植瘤中均有VEGF蛋白的表达,其中对照组VEGF蛋白的平均染色强度(IS)为2.20±0.40,明显高于RGZ组(1.48±0.37,P＜0.01)；RGZ+ATRA组的IS为0.58 ±0.26,明显低于RGZ组(P＜0.01).各组裸鼠移植瘤中均有CD34的表达,其中对照组CD34表达最强,微血管密度(MVD)为(56.4±15.2)个/高倍视野,明显高于RGZ组[(44.6±11.2)个/高倍视野,P＜0.05]；RGZ+ ATRA组CD34表达最弱,MVD为(21.5±8.6)个/高倍视野,明显低于RGZ组(P＜0.01).结论 RGZ和ATRA在体内环境中也能发挥抑制骨髓瘤细胞增殖和生长的作用.通过抑制骨髓瘤细胞中VEGF 的表达从而阻断血管形成,可能也是RGZ和ATRA抗肿瘤作用的重要机制之一.
目的 研究囉格列酮(RGZ)和全反式維甲痠(ATRA)對多髮性骨髓瘤裸鼠移植瘤生長和血管形成的影響.方法 分彆以不同濃度的RGZ和ATRA或RGZ+ ATRA處理U266細胞24h,採用半定量RT-PCR法檢測各組U266細胞中血管內皮細胞生長因子(VEGF)的錶達.將U266細胞接種于4週齡Balb/c裸鼠一側肩胛部皮下,接種1週後分彆以RGZ和RGZ+ ATRA腹腔註射榦預,連續給藥21 d.第21天處死裸鼠,剝離皮下腫瘤併稱重,將腫瘤組織分彆進行HE和CD34、VEGF免疫組化染色.結果 未經處理的對照組U266細胞中VEGF mRNA高錶達；經RGZ處理後,VEGF mRNA的錶達水平下調；經RGZ+ ATRA處理後,VEGF mRNA的錶達水平較RGZ組更低.U266細胞接種後,在裸鼠皮下均可形成腫瘤.腹腔用藥後,RGZ組裸鼠移植瘤的體積和重量分彆為(785±262)mm3和(1748±365)mg,均明顯低于對照組(均P＜0.01)；RGZ+ ATRA組移植瘤的體積和重量分彆為(154±89)mm3和(626±102) mg,均明顯低于RGZ組(均P＜0.05).各組裸鼠移植瘤中均有VEGF蛋白的錶達,其中對照組VEGF蛋白的平均染色彊度(IS)為2.20±0.40,明顯高于RGZ組(1.48±0.37,P＜0.01)；RGZ+ATRA組的IS為0.58 ±0.26,明顯低于RGZ組(P＜0.01).各組裸鼠移植瘤中均有CD34的錶達,其中對照組CD34錶達最彊,微血管密度(MVD)為(56.4±15.2)箇/高倍視野,明顯高于RGZ組[(44.6±11.2)箇/高倍視野,P＜0.05]；RGZ+ ATRA組CD34錶達最弱,MVD為(21.5±8.6)箇/高倍視野,明顯低于RGZ組(P＜0.01).結論 RGZ和ATRA在體內環境中也能髮揮抑製骨髓瘤細胞增殖和生長的作用.通過抑製骨髓瘤細胞中VEGF 的錶達從而阻斷血管形成,可能也是RGZ和ATRA抗腫瘤作用的重要機製之一.
목적 연구라격렬동(RGZ)화전반식유갑산(ATRA)대다발성골수류라서이식류생장화혈관형성적영향.방법 분별이불동농도적RGZ화ATRA혹RGZ+ ATRA처리U266세포24h,채용반정량RT-PCR법검측각조U266세포중혈관내피세포생장인자(VEGF)적표체.장U266세포접충우4주령Balb/c라서일측견갑부피하,접충1주후분별이RGZ화RGZ+ ATRA복강주사간예,련속급약21 d.제21천처사라서,박리피하종류병칭중,장종류조직분별진행HE화CD34、VEGF면역조화염색.결과 미경처리적대조조U266세포중VEGF mRNA고표체；경RGZ처리후,VEGF mRNA적표체수평하조；경RGZ+ ATRA처리후,VEGF mRNA적표체수평교RGZ조경저.U266세포접충후,재라서피하균가형성종류.복강용약후,RGZ조라서이식류적체적화중량분별위(785±262)mm3화(1748±365)mg,균명현저우대조조(균P＜0.01)；RGZ+ ATRA조이식류적체적화중량분별위(154±89)mm3화(626±102) mg,균명현저우RGZ조(균P＜0.05).각조라서이식류중균유VEGF단백적표체,기중대조조VEGF단백적평균염색강도(IS)위2.20±0.40,명현고우RGZ조(1.48±0.37,P＜0.01)；RGZ+ATRA조적IS위0.58 ±0.26,명현저우RGZ조(P＜0.01).각조라서이식류중균유CD34적표체,기중대조조CD34표체최강,미혈관밀도(MVD)위(56.4±15.2)개/고배시야,명현고우RGZ조[(44.6±11.2)개/고배시야,P＜0.05]；RGZ+ ATRA조CD34표체최약,MVD위(21.5±8.6)개/고배시야,명현저우RGZ조(P＜0.01).결론 RGZ화ATRA재체내배경중야능발휘억제골수류세포증식화생장적작용.통과억제골수류세포중VEGF 적표체종이조단혈관형성,가능야시RGZ화ATRA항종류작용적중요궤제지일.
Objective To observe the effect of rosiglitazone (RGZ) and all-trans-retinoic acid (ATRA) on the growth of myeloma xenograft in nude mice and to explore the influence of RGZ and ATRA on VEGF expression and angiogenesis in the tumor.Methods VEGF gene expression in myeloma cell line U266 cells was analyzed by semi-quantitative RT-PCR after incubation with RGZ,ATRA,or RGZ + ATRA for 24 h.Myeloma xenograft was established by subcutaneous injection of 107 U266 cells in the scapula area of 4-week old nude mice.7 days later,the nude mice were administered with RGZ,ATRA or RGZ + ATRA,respectively,by intraperitoneal injection once every day for 21 days.The control mice wcre given equal volume of normal saline instead of the drug.On the 21 st day of treatment,the mice were sacrificed and the tumors were taken off,and the tumor volume and weight were measured.The tumors were examined by h istopathology with HE staining,and microvessel density (MVD),CD34 and VEGF expression in the tumors were analyzed by immunohistochemical staining.Results VEGF mRNA was highly expressed in U266 cells and was decreased in a dose-dependent manner after incubation with RGZ.The VEGF mRNA level was further more decreased after RGZ + ATRA treatment.Xenografts of U266 cells were developed in all nude mice.The volume and weight of xenografts in the RGZ group were (785 ± 262) mm3 and (1748 ± 365) mg,respectively,significantly lower than those of the control group (both P ＜ 0.01).More significant inhibition was in the RGZ + ATRA group,(154 ± 89) mm3 and (626 ± 102) mg,respectively,both were P ＜ 0.05 vs.the RGZ group.RGZ inhibited the angiogenesis in U266 xenografts and immunohistochemical staining showed that the tumor MVD and VEGF expression were significantly decreased by RGZ treatment,and further more inhibited in the RGZ + ATRA group.VEGF protein was expressed in all xenografts in the nude mice.Its immunohistochemical staining intensity was 2.20 ± 0.40 in the control group,significantly higher than that of 1.48 ± 0.37 in the RGZ group (P ＜ 0.01),and that of RGZ + ATRA group was 0.58 ± 0.26,further significantly lower than that of the RGZ group (P ＜ 0.01).CD34 was expressed in all xenografts,most highly in the control group and lowest in the RGZ + ATRA group.The microvessel density (MVD) was highest in the control group (56.4 ± 15.2),significantly lower in the RGZ group (44.6 ± 11.2)(P＜0.05),and lowest in the RGZ +ATRA group (21.5 ±8.6,P＜0.01).Conclusions The growth of myeloma cells can also be inhibited by RGZ and ATRA in nude mice in vivo.In addition to differentiation and apoptosis induction,RGZ can inhibit the formation of myeloma xenograft probably also through the downregulation of VEGF expression and subsequent angiogenesis.
