中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
Chinese Journal of Oncology
2015年
11期
810-815
,共6页
马家驰%陈泉%顾远晖%李一平%房伟%刘美玲%陈晓昌%郭庆金%马世勋
馬傢馳%陳泉%顧遠暉%李一平%房偉%劉美玲%陳曉昌%郭慶金%馬世勛
마가치%진천%고원휘%리일평%방위%류미령%진효창%곽경금%마세훈
结肠肿瘤%白细胞介素1α%内皮细胞%细胞增殖%细胞迁移
結腸腫瘤%白細胞介素1α%內皮細胞%細胞增殖%細胞遷移
결장종류%백세포개소1α%내피세포%세포증식%세포천이
Colonic neoplasms%Interleukin-1α%Endothelial cells%Cell proliferation%Cell movement
目的 探讨结肠癌细胞起源的白细胞介素1α(IL-1α)及其受体拮抗剂IL-1ra对血管内皮细胞的影响.方法 Western blot法检测IL-1α和IL-1 Ⅰ型受体(IL-1R1)在结肠癌细胞中的表达,细胞增殖和迁移实验检测外源性的IL-1α和IL-1ra对胎儿脐静脉内皮细胞(HUVEC)增殖和迁移的影响;采用双层培养系统检测肿瘤细胞起源的IL-1α对血管内皮细胞增殖和迁移的影响,以及IL-1ra对血管内皮细胞的作用.结果 Western blot检测显示,IL-1α蛋白在高肝转移结肠癌HT-29和WiDr细胞中表达,而在低肝转移结肠癌CaCo-2和CoLo320细胞中不表达.细胞迁移实验显示,对照组、1 ng/mlrIL-1α组、10 ng/ml rIL-1α组和100 ng/ml rIL-1o组的穿膜细胞数分别为(17.9±3.6)个、(23.2±4.2)个、(31.7±4.5)个和(38.6±4.9)个,IL-1α能够显著提高HUVEC的迁移能力,并与IL-1α浓度有关(均P＜0.01).细胞增殖实验显示,对照组、1 ng/ml rIL-1α组、10 ng/ml rIL-1α组和100 ng/ml rIL-1α组的吸光度值分别为1.37±0.18、1.79±0.14、2.14±0.17和2.21±0.23,IL-1α能够显著提高HUVEC的增殖能力,并与IL-1α浓度有关(均P＜0.01).IL-1ra能够抑制HUVEC的迁移和增殖(均P＜0.01).在共同培养系统中,对照组、HUVECs+ 10 pg/ml rIL-1α组和HUVECs+HT-29组中血管内皮生长因子(VEGF)水平分别为(1.697± 0.072) ng/ml、(3.507±0.064) ng/ml和(4.139±0.039) ng/ml,HUVECs+ 10 pg/mlrIL-1α组和HUVECs+HT-29组分别与HUVECs组比较,差异均有统计学意义(均P＜0.01).结论 结肠癌细胞起源的IL-1α在结肠癌的转移过程中有重要作用,其通过结合IL-1R1提高结肠癌细胞VEGF的分泌水平,强化血管内皮细胞的增殖和迁移,进而促进肿瘤的新生血管;而IL-1ra具有抑制IL-1α水平的作用,从而抑制结肠癌的新生血管.
目的 探討結腸癌細胞起源的白細胞介素1α(IL-1α)及其受體拮抗劑IL-1ra對血管內皮細胞的影響.方法 Western blot法檢測IL-1α和IL-1 Ⅰ型受體(IL-1R1)在結腸癌細胞中的錶達,細胞增殖和遷移實驗檢測外源性的IL-1α和IL-1ra對胎兒臍靜脈內皮細胞(HUVEC)增殖和遷移的影響;採用雙層培養繫統檢測腫瘤細胞起源的IL-1α對血管內皮細胞增殖和遷移的影響,以及IL-1ra對血管內皮細胞的作用.結果 Western blot檢測顯示,IL-1α蛋白在高肝轉移結腸癌HT-29和WiDr細胞中錶達,而在低肝轉移結腸癌CaCo-2和CoLo320細胞中不錶達.細胞遷移實驗顯示,對照組、1 ng/mlrIL-1α組、10 ng/ml rIL-1α組和100 ng/ml rIL-1o組的穿膜細胞數分彆為(17.9±3.6)箇、(23.2±4.2)箇、(31.7±4.5)箇和(38.6±4.9)箇,IL-1α能夠顯著提高HUVEC的遷移能力,併與IL-1α濃度有關(均P＜0.01).細胞增殖實驗顯示,對照組、1 ng/ml rIL-1α組、10 ng/ml rIL-1α組和100 ng/ml rIL-1α組的吸光度值分彆為1.37±0.18、1.79±0.14、2.14±0.17和2.21±0.23,IL-1α能夠顯著提高HUVEC的增殖能力,併與IL-1α濃度有關(均P＜0.01).IL-1ra能夠抑製HUVEC的遷移和增殖(均P＜0.01).在共同培養繫統中,對照組、HUVECs+ 10 pg/ml rIL-1α組和HUVECs+HT-29組中血管內皮生長因子(VEGF)水平分彆為(1.697± 0.072) ng/ml、(3.507±0.064) ng/ml和(4.139±0.039) ng/ml,HUVECs+ 10 pg/mlrIL-1α組和HUVECs+HT-29組分彆與HUVECs組比較,差異均有統計學意義(均P＜0.01).結論 結腸癌細胞起源的IL-1α在結腸癌的轉移過程中有重要作用,其通過結閤IL-1R1提高結腸癌細胞VEGF的分泌水平,彊化血管內皮細胞的增殖和遷移,進而促進腫瘤的新生血管;而IL-1ra具有抑製IL-1α水平的作用,從而抑製結腸癌的新生血管.
목적 탐토결장암세포기원적백세포개소1α(IL-1α)급기수체길항제IL-1ra대혈관내피세포적영향.방법 Western blot법검측IL-1α화IL-1 Ⅰ형수체(IL-1R1)재결장암세포중적표체,세포증식화천이실험검측외원성적IL-1α화IL-1ra대태인제정맥내피세포(HUVEC)증식화천이적영향;채용쌍층배양계통검측종류세포기원적IL-1α대혈관내피세포증식화천이적영향,이급IL-1ra대혈관내피세포적작용.결과 Western blot검측현시,IL-1α단백재고간전이결장암HT-29화WiDr세포중표체,이재저간전이결장암CaCo-2화CoLo320세포중불표체.세포천이실험현시,대조조、1 ng/mlrIL-1α조、10 ng/ml rIL-1α조화100 ng/ml rIL-1o조적천막세포수분별위(17.9±3.6)개、(23.2±4.2)개、(31.7±4.5)개화(38.6±4.9)개,IL-1α능구현저제고HUVEC적천이능력,병여IL-1α농도유관(균P＜0.01).세포증식실험현시,대조조、1 ng/ml rIL-1α조、10 ng/ml rIL-1α조화100 ng/ml rIL-1α조적흡광도치분별위1.37±0.18、1.79±0.14、2.14±0.17화2.21±0.23,IL-1α능구현저제고HUVEC적증식능력,병여IL-1α농도유관(균P＜0.01).IL-1ra능구억제HUVEC적천이화증식(균P＜0.01).재공동배양계통중,대조조、HUVECs+ 10 pg/ml rIL-1α조화HUVECs+HT-29조중혈관내피생장인자(VEGF)수평분별위(1.697± 0.072) ng/ml、(3.507±0.064) ng/ml화(4.139±0.039) ng/ml,HUVECs+ 10 pg/mlrIL-1α조화HUVECs+HT-29조분별여HUVECs조비교,차이균유통계학의의(균P＜0.01).결론 결장암세포기원적IL-1α재결장암적전이과정중유중요작용,기통과결합IL-1R1제고결장암세포VEGF적분비수평,강화혈관내피세포적증식화천이,진이촉진종류적신생혈관;이IL-1ra구유억제IL-1α수평적작용,종이억제결장암적신생혈관.
Objective To explore the effect of colon cancer cell-derived interleukin-1α on the migration and proliferation of human umbilical vein endothelial cells as well as the role of IL-1α and IL-1ra in the angiogenesis process.Methods Western blot was used to detect the expression of IL-1α and IL-1R1 protein in the colon cancer cell lines with different liver metastatic potential.We also examined how IL-1α and IL-1ra influence the proliferation and migration of umbilical vascular endothelial cells assessed by PreMix WST-1 assay and migration assay, respectively.Double layer culture technique was used to detect the effect of IL-1α on the proliferation and migration of vascular endothelial cells and the effect of IL-1ra on the vascular endothelial cells.Results Western blot analysis showed that IL-1α protein was only detected in highly metastatic colon cancer HT-29 and WiDr cells, but not in the lowly metastatic CaCo-2 and CoLo320 cells.Migration assay showed that there were significant differences in the number of penetrated cells between the control (17.9±3.6) and 1 ng/ml rIL-1α group (23.2±4.2), 10 ng/ml rIL-1α group (31.7±4.5), and 100 ng/ml rIL-1α group (38.6 ±4.9), showing that it was positively correlated with the increasing concentration of rIL-1α (P＜0.01 for all).The proliferation assay showed that the absorbance values were 1.37±0.18 in the control group, and 1.79±0.14 in the 1 ng/ml rIL-1α group, 2.14±0.17 in the 10 ng/ml rIL-1α group, and 2.21±0.23 in the 100 ng/ml rIL-1α group, showing a positive correlation with the increasing concentration of rIL-1αt (P＜0.01 for all).IL-1ra significantly inhibited the proliferation and migration of vascular endothelial cells (P＜0.01).The levels of VEGF protein were (1.697±0.072) ng/ml, (3.507±0.064) ng/ml and (4.139±0.039) ng/ml in the control, HUVECs+IL-1α and HUVECs+HT-29 coculture system groups, respectively, showing a significant difference between the control and HUVECs+ 10 pg/ml rIL-1α groups and between the control and HUVECs+HT-29 groups (P＜0.01 for both).Conclusions Our findings indicate that colon cancer cell-derived IL-1α plays an important role in the liver metastasis of colon cancer through increased VEGF level of the colon cancer cells and enhanced vascular endothelial cells proliferation, migration and angiogenesis, while IL-1ra can suppress the effect of IL-1α and inhibit the angiogenesis in colon cancer.
