临床肿瘤学杂志
臨床腫瘤學雜誌
림상종류학잡지
CHINESE CLINICAL ONCOLOGY
2015年
4期
296-302
,共7页
孙荣%高舒%华海清%杨爱珍%秦叔逵
孫榮%高舒%華海清%楊愛珍%秦叔逵
손영%고서%화해청%양애진%진숙규
肝癌%人参皂苷Rg3%索拉非尼%奥沙利铂%血管生成
肝癌%人參皂苷Rg3%索拉非尼%奧沙利鉑%血管生成
간암%인삼조감Rg3%색랍비니%오사리박%혈관생성
Hepacarcinoma%Ginsenoside Rg3%Sorafenib%Oxaliplatin%Angiogenesis
目的：观察人参皂苷Rg3、索拉非尼、奥沙利铂单药及联合对裸鼠人肝癌细胞移植瘤血管生成的作用并探讨其可能机制。方法以裸鼠人肝癌转移模型LCI?D20为观察对象，将60只荷瘤裸鼠随机分成8组，分别为人参皂苷Rg3组（ A组）、奥沙利铂组（ B组）、索拉非尼组（ C组）、人参皂苷Rg3＋索拉非尼组（ D组）、人参皂苷Rg3＋奥沙利铂组（ E组）、奥沙利铂＋索拉非尼组（ F组）、人参皂苷Rg3＋奥沙利铂＋索拉非尼组（ G组）和生理盐水对照组（ H组）。肿瘤接种第11 d后开始给药，人参皂苷Rg35 mg／kg（1天1次）、奥沙利铂5 mg／kg（2天1次），均用腹腔注射，索拉非尼30 mg／kg（1天1次）灌胃。给药14 d后处死裸鼠，剥离瘤体，检测各组瘤组织中微血管密度（ MVD），免疫组化染色和Western blotting检测各组瘤组织中血管内皮生长因子（ VEGF）、缺氧诱导因子（ HIF）?1α和VEGF受体（ VEGFR）?2的表达。结果与H组比较，其余各组MVD均较低（ P＜0?01），VEGF蛋白阳性表达率均较低（ P＜0?05），HIF?1α蛋白阳性表达率均下降，但差异无统计学意义（ P＞0?05）；A组、D组、E组的VEGFR?2蛋白阳性表达率显著低于H组（ P＜0?05）。与H组比较，仅A组、B组、C组、D组、E组能显著下调瘤组织中VEGF、HIF?1α和VEGFR?2蛋白的表达（ P＜0?05）。结论人参皂苷Rg3具有一定的抗血管生成作用，其机制可能与下调VEGF、HIF?1α、VEGFR?2及MVD的表达有关。人参皂苷Rg3分别与索拉非尼、奥沙利铂联合可以增强抗血管生成作用，但三药联合时抗血管生成作用反而减弱，提示可能存在其他抗肿瘤机制，值得进一步研究。
目的：觀察人參皂苷Rg3、索拉非尼、奧沙利鉑單藥及聯閤對裸鼠人肝癌細胞移植瘤血管生成的作用併探討其可能機製。方法以裸鼠人肝癌轉移模型LCI?D20為觀察對象，將60隻荷瘤裸鼠隨機分成8組，分彆為人參皂苷Rg3組（ A組）、奧沙利鉑組（ B組）、索拉非尼組（ C組）、人參皂苷Rg3＋索拉非尼組（ D組）、人參皂苷Rg3＋奧沙利鉑組（ E組）、奧沙利鉑＋索拉非尼組（ F組）、人參皂苷Rg3＋奧沙利鉑＋索拉非尼組（ G組）和生理鹽水對照組（ H組）。腫瘤接種第11 d後開始給藥，人參皂苷Rg35 mg／kg（1天1次）、奧沙利鉑5 mg／kg（2天1次），均用腹腔註射，索拉非尼30 mg／kg（1天1次）灌胃。給藥14 d後處死裸鼠，剝離瘤體，檢測各組瘤組織中微血管密度（ MVD），免疫組化染色和Western blotting檢測各組瘤組織中血管內皮生長因子（ VEGF）、缺氧誘導因子（ HIF）?1α和VEGF受體（ VEGFR）?2的錶達。結果與H組比較，其餘各組MVD均較低（ P＜0?01），VEGF蛋白暘性錶達率均較低（ P＜0?05），HIF?1α蛋白暘性錶達率均下降，但差異無統計學意義（ P＞0?05）；A組、D組、E組的VEGFR?2蛋白暘性錶達率顯著低于H組（ P＜0?05）。與H組比較，僅A組、B組、C組、D組、E組能顯著下調瘤組織中VEGF、HIF?1α和VEGFR?2蛋白的錶達（ P＜0?05）。結論人參皂苷Rg3具有一定的抗血管生成作用，其機製可能與下調VEGF、HIF?1α、VEGFR?2及MVD的錶達有關。人參皂苷Rg3分彆與索拉非尼、奧沙利鉑聯閤可以增彊抗血管生成作用，但三藥聯閤時抗血管生成作用反而減弱，提示可能存在其他抗腫瘤機製，值得進一步研究。
목적：관찰인삼조감Rg3、색랍비니、오사리박단약급연합대라서인간암세포이식류혈관생성적작용병탐토기가능궤제。방법이라서인간암전이모형LCI?D20위관찰대상，장60지하류라서수궤분성8조，분별위인삼조감Rg3조（ A조）、오사리박조（ B조）、색랍비니조（ C조）、인삼조감Rg3＋색랍비니조（ D조）、인삼조감Rg3＋오사리박조（ E조）、오사리박＋색랍비니조（ F조）、인삼조감Rg3＋오사리박＋색랍비니조（ G조）화생리염수대조조（ H조）。종류접충제11 d후개시급약，인삼조감Rg35 mg／kg（1천1차）、오사리박5 mg／kg（2천1차），균용복강주사，색랍비니30 mg／kg（1천1차）관위。급약14 d후처사라서，박리류체，검측각조류조직중미혈관밀도（ MVD），면역조화염색화Western blotting검측각조류조직중혈관내피생장인자（ VEGF）、결양유도인자（ HIF）?1α화VEGF수체（ VEGFR）?2적표체。결과여H조비교，기여각조MVD균교저（ P＜0?01），VEGF단백양성표체솔균교저（ P＜0?05），HIF?1α단백양성표체솔균하강，단차이무통계학의의（ P＞0?05）；A조、D조、E조적VEGFR?2단백양성표체솔현저저우H조（ P＜0?05）。여H조비교，부A조、B조、C조、D조、E조능현저하조류조직중VEGF、HIF?1α화VEGFR?2단백적표체（ P＜0?05）。결론인삼조감Rg3구유일정적항혈관생성작용，기궤제가능여하조VEGF、HIF?1α、VEGFR?2급MVD적표체유관。인삼조감Rg3분별여색랍비니、오사리박연합가이증강항혈관생성작용，단삼약연합시항혈관생성작용반이감약，제시가능존재기타항종류궤제，치득진일보연구。
Objective To observe the effect of ginsenoside Rg3,sorafenib, oxaliplatin alone or with different combination in neovascularization of tumor in nude mice with human hepatocellular carcinoma, and investigate the possible mechanisms. Methods Sixty nude mice with high metastatic human hepatocellular carcinoma transplanted in situ( LCI?D20) were randomly divided into gin?senoside Rg3 group(Group A), oxaliplatin group(Group B), sorafenib group(Group C), ginsenoside Rg3+ sorafenib group(Group D), ginsenoside Rg3+oxaliplatin group(Group E), oxaliplatin+sorafenib group(Group F), ginsenoside Rg3+ oxaliplatin+sorafenib group( Group G) and formal saline group( Group H) . The drug was administered eleven days later after the inoculation of tumor. The dosage of the medicine was as follows: ginsenoside Rg3(5mg/kg, qd, 14 days, intraperitoneal injection) and oxaliplatin(5mg/kg, q2d, 14 days, intraperitoneal injection) and sorafenib( 30mg/kg, qd, 14 days, gastric lavage) . All mice were sacrificed at 14 days af?ter administration, and tumor tissues were resected. Immunohistochemical method and Western blotting were used to detect the expres?sion rate and relative quantity of vascular endothelial growth factor( VEGF) , hypoxia?inducible factor( HIF)?1α, VEGF receptor( VEG?FR)?2 and micro?vessel density( MVD) in the tumor. Results The treatment groups presented different degrees of MVD lower than that of Group H( P<0?01) . Positive expression rates of VEGF in all treatment groups were decreased significantly compared with the Group H(P<0?05). Compared with Group H, positive expression rates of HIF?1α had a overall downward trend(P>0?05).The positive expression rates of VEGFR?2 in Group A, D and E were decreased significantly than that in Group H(P<0?05). Relative quantity of VEGF, HIF?1α and VEGFR?2 in Group A, B, C,D and E were decreased significantly than those in Group H( P<0?05) . Conclusion Ginsenoside Rg3 has an anti?angiogenic effect. Its anti?angiogenic effect might be related to the down?regulated expression of VEGF, HIF?1α and VEGFR?2. Ginsenoside Rg3 in combination with oxaliplatin or sorafenib can enhance the anti?angiogenic effect, but the expression of VEGF, HIF?1α and VEGFR?2 protein didn?t decreased significantly in the combination of three drugs. It shows that the antitumor effect of three drugs may still relate other mechanisms, which needed further study.
