中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2010年
11期
808-812
,共5页
索拉非尼%胆管肿瘤%淋巴管生成%淋巴管内皮透明质酸盐受体1%血管内皮细胞生长因子受体3
索拉非尼%膽管腫瘤%淋巴管生成%淋巴管內皮透明質痠鹽受體1%血管內皮細胞生長因子受體3
색랍비니%담관종류%림파관생성%림파관내피투명질산염수체1%혈관내피세포생장인자수체3
Sorafenib%Bile duct neoplasms%Lymphangiogenesis%Lyve-1%VEGFR-3
目的 探讨索拉非尼对胆管癌移植瘤淋巴管生成的影响.方法 对Bal B/c-nu裸鼠皮下接种胆管癌QBC939细胞,构建裸鼠移植瘤模型.成瘤后,随机将36只裸鼠分为对照组、索拉非尼30 mg·kg-1·d-1组和索拉非尼60 mg·kg-1·d-1组,每组12只,灌胃法连续给药6周,观察各组裸鼠移植瘤的生长情况.以淋巴管内皮透明质酸盐受体1(LYVE-1)标记肿瘤周边淋巴管,并计数微淋巴管密度(LMVD).以逆转录聚合酶链反应(RT-PCR)法检测肿瘤周边组织中血管内皮细胞生长因子受体3(VEGFR-3)mRNA的表达.结果 索拉非尼能显著抑制胆管癌移植瘤的生长,索拉非尼30 mg·kg-1·d-1组和60 mg·kg-1·d-1组的抑瘤率分别为55.1%和67.9%.对照组、索拉非尼30 mg·kg-1·d-1组和60 mg·kg-1·d-1组裸鼠移植瘤周边组织的LMVD分别为11.75±3.19、6.84±2.18和5.03±1.91.对照组的LMVD明显高于两个用药组(P＜0.01).对照组、索拉非尼30 mg·kg-1·d-1组和60 mg·kg-1·d-1组裸鼠移植瘤周边组织中VEGFR-3 mRNA的相对表达量分别为2.158±0.312、1.027±0.144和0.736±0.149,对照组中VEGFR-3 mRNA的相对表达量明显高于两个用药组(P＜0.05).各组裸鼠胆管癌区域引流淋巴结中均未观察到胆管癌转移灶.结论 索拉非尼能显著抑制胆管癌裸鼠移植瘤的生长.索拉非尼可能通过抑制胆管癌周边组织中VEGF-C/VEGF-D/VEGFR-3轴的表达,来降低LMVD.
目的 探討索拉非尼對膽管癌移植瘤淋巴管生成的影響.方法 對Bal B/c-nu裸鼠皮下接種膽管癌QBC939細胞,構建裸鼠移植瘤模型.成瘤後,隨機將36隻裸鼠分為對照組、索拉非尼30 mg·kg-1·d-1組和索拉非尼60 mg·kg-1·d-1組,每組12隻,灌胃法連續給藥6週,觀察各組裸鼠移植瘤的生長情況.以淋巴管內皮透明質痠鹽受體1(LYVE-1)標記腫瘤週邊淋巴管,併計數微淋巴管密度(LMVD).以逆轉錄聚閤酶鏈反應(RT-PCR)法檢測腫瘤週邊組織中血管內皮細胞生長因子受體3(VEGFR-3)mRNA的錶達.結果 索拉非尼能顯著抑製膽管癌移植瘤的生長,索拉非尼30 mg·kg-1·d-1組和60 mg·kg-1·d-1組的抑瘤率分彆為55.1%和67.9%.對照組、索拉非尼30 mg·kg-1·d-1組和60 mg·kg-1·d-1組裸鼠移植瘤週邊組織的LMVD分彆為11.75±3.19、6.84±2.18和5.03±1.91.對照組的LMVD明顯高于兩箇用藥組(P＜0.01).對照組、索拉非尼30 mg·kg-1·d-1組和60 mg·kg-1·d-1組裸鼠移植瘤週邊組織中VEGFR-3 mRNA的相對錶達量分彆為2.158±0.312、1.027±0.144和0.736±0.149,對照組中VEGFR-3 mRNA的相對錶達量明顯高于兩箇用藥組(P＜0.05).各組裸鼠膽管癌區域引流淋巴結中均未觀察到膽管癌轉移竈.結論 索拉非尼能顯著抑製膽管癌裸鼠移植瘤的生長.索拉非尼可能通過抑製膽管癌週邊組織中VEGF-C/VEGF-D/VEGFR-3軸的錶達,來降低LMVD.
목적 탐토색랍비니대담관암이식류림파관생성적영향.방법 대Bal B/c-nu라서피하접충담관암QBC939세포,구건라서이식류모형.성류후,수궤장36지라서분위대조조、색랍비니30 mg·kg-1·d-1조화색랍비니60 mg·kg-1·d-1조,매조12지,관위법련속급약6주,관찰각조라서이식류적생장정황.이림파관내피투명질산염수체1(LYVE-1)표기종류주변림파관,병계수미림파관밀도(LMVD).이역전록취합매련반응(RT-PCR)법검측종류주변조직중혈관내피세포생장인자수체3(VEGFR-3)mRNA적표체.결과 색랍비니능현저억제담관암이식류적생장,색랍비니30 mg·kg-1·d-1조화60 mg·kg-1·d-1조적억류솔분별위55.1%화67.9%.대조조、색랍비니30 mg·kg-1·d-1조화60 mg·kg-1·d-1조라서이식류주변조직적LMVD분별위11.75±3.19、6.84±2.18화5.03±1.91.대조조적LMVD명현고우량개용약조(P＜0.01).대조조、색랍비니30 mg·kg-1·d-1조화60 mg·kg-1·d-1조라서이식류주변조직중VEGFR-3 mRNA적상대표체량분별위2.158±0.312、1.027±0.144화0.736±0.149,대조조중VEGFR-3 mRNA적상대표체량명현고우량개용약조(P＜0.05).각조라서담관암구역인류림파결중균미관찰도담관암전이조.결론 색랍비니능현저억제담관암라서이식류적생장.색랍비니가능통과억제담관암주변조직중VEGF-C/VEGF-D/VEGFR-3축적표체,래강저LMVD.
Objective To study the effects of sorafenib on lymphangiogenesis in transplanted human cholangiocarcinoma in nude mice. Methods The model of transplanted human cholangiocarcinoma in nude mice was estabished by subcutaneous inoculation of cholangiocarcinoma cell line QBC 939 cells. Thirty-six nude mice were randomly divided into 3 groups after tumor formation: control group, sorafenib 30 mg· kg-1 · d-1 group and sorafenib 60 mg· kg-1 · d-1 group (n =12 each), and then treated by gavage for6 weeks. The tumor growth of the dose groups and control group was measured with calipers. Using immunohistochemical staining, the lymphatic microvessels at tumor edge were marked by LYVE-1 and counted. The expression of VEGFR-3 mRNA in paracancerous tissues was evaluated by RT-PCR. Results Sorafenib significantly depressed the growth of cholangiocarcinoma. The inhibitory rate in the sorafenib 30 mg · kg-1 · d-1 group and 60 mg· kg-1 · d-1 group was 55.1％ and 67.9％, respectively. The LMVDs of the control group,sorafenib 30 mg · kg-1 · d-1 group and 60 mg· kg-1 · d-1 group were 11.75 ±3.19, 6.84 ±2. 18 and 5.03 ±1.91, respectively. The LMVD of the control group was significantly higher than that in the dose groups ( P ＜ 0. 01 ). The relative expressions of VEGFR-3 mRNA in the control group, sorafenib 30 mg· kg-1 · d-1 group and 60 mg· kg-1 · d -1 group were 2. 158 ±0. 312, 1. 027 ±0. 144 and 0. 736 ±0. 149, respectively. The relative expression of VEGFR-3 mRNA in the control group was significantly higher than that in the dose groups (P ＜ 0. 05). No occurrence of lymph node metastasis was found in all groups.Conclusion Sorafenib can significantly inhibit the growth of xenograft cholangiocarcinoma in nude mice.Sorafenib may reduce LMVD by down-regulation of the expression of VEGF-C/D and VEGFR-3 signaling axis.
