中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2010年
2期
123-127
,共5页
夏启胜%石垣靖人%孙立%陈瑞%元雄良治
夏啟勝%石垣靖人%孫立%陳瑞%元雄良治
하계성%석원정인%손립%진서%원웅량치
抗肿瘤药%胰腺肿瘤%微RNAs%B细胞整合簇
抗腫瘤藥%胰腺腫瘤%微RNAs%B細胞整閤簇
항종류약%이선종류%미RNAs%B세포정합족
Antineoplastic agents%Pancreatic neoplasms%MicroRNAs%B-cell integration cluster
目的 了解抗癌药物对人胰腺癌细胞小分子RNA 155(miR-155)及其前体B细胞整合簇(BIC)RNA表达的影响.方法 人胰腺癌PANC-1细胞分别给予吉西他滨等抗癌药物处理后,实时定量RT-PCR测定BIC RNA和成熟的miR-155表达变化情况.应用磷脂酰肌醇-3激酶(PI3K)相关激酶抑制剂渥曼青霉素了解PI3K相关激酶是否与BIC RNA的调节有关.结果 经抗癌药物处理后,PANC-1细胞内BIC RNA表达显著上调,1.0、2.5、5.0、10.0 mg/L吉西他滨处理后48 h BIC RNA 的表达量分别是37.1 ±4.1、29.0±5.7、21.0±7.6、40.4.±9.0,均高于对照组(1.6±1.1,均P＜0.05);处理后72 h BIC RNA表达分别为27.7 ±3.1、43.1 ±1.2、31.8±5.4、23.1±1.4,均明显高于对照组(1.0±0.1,均P＜0.05),10 mg/L 5-氟尿嘧啶和100 mg/L博来霉素处理后48 h,BIC RNA表达分别为5.2±1.1和11.5±0.7,均高于对照组(1.7±0.7,均P＜0.05).各浓度吉西他滨处理后48h,PANC-1细胞内miR-155水平与对照组比差异无统计学意义(P＞0.05),但处理后72 h,miR-155水平高于对照组(2.21±0.40、1.86±0.03、2.47±0.04、3.24±0.05比1.11±0.09,P＜0.05).吉西他滨诱导的BIC RNA上调可以被渥曼青霉素抑制,1μmol/L渥曼青霉素+5 mg/L吉西他滨组和10μmol/L渥曼青霉素+5 mg/L吉西他滨组BIC RNA表达均低于5 mg/L吉西他滨组(5.34±1.11、1.26±0.07比11.82±3.11,均P＜0.05).结论 抗癌药物处理能明显诱导人胰腺癌PANC-1细胞BIC RNA上调,并引起成熟miR-155上调,吉西他滨诱导的BIC RNA上调与PI3K信号通路相关.
目的 瞭解抗癌藥物對人胰腺癌細胞小分子RNA 155(miR-155)及其前體B細胞整閤簇(BIC)RNA錶達的影響.方法 人胰腺癌PANC-1細胞分彆給予吉西他濱等抗癌藥物處理後,實時定量RT-PCR測定BIC RNA和成熟的miR-155錶達變化情況.應用燐脂酰肌醇-3激酶(PI3K)相關激酶抑製劑渥曼青黴素瞭解PI3K相關激酶是否與BIC RNA的調節有關.結果 經抗癌藥物處理後,PANC-1細胞內BIC RNA錶達顯著上調,1.0、2.5、5.0、10.0 mg/L吉西他濱處理後48 h BIC RNA 的錶達量分彆是37.1 ±4.1、29.0±5.7、21.0±7.6、40.4.±9.0,均高于對照組(1.6±1.1,均P＜0.05);處理後72 h BIC RNA錶達分彆為27.7 ±3.1、43.1 ±1.2、31.8±5.4、23.1±1.4,均明顯高于對照組(1.0±0.1,均P＜0.05),10 mg/L 5-氟尿嘧啶和100 mg/L博來黴素處理後48 h,BIC RNA錶達分彆為5.2±1.1和11.5±0.7,均高于對照組(1.7±0.7,均P＜0.05).各濃度吉西他濱處理後48h,PANC-1細胞內miR-155水平與對照組比差異無統計學意義(P＞0.05),但處理後72 h,miR-155水平高于對照組(2.21±0.40、1.86±0.03、2.47±0.04、3.24±0.05比1.11±0.09,P＜0.05).吉西他濱誘導的BIC RNA上調可以被渥曼青黴素抑製,1μmol/L渥曼青黴素+5 mg/L吉西他濱組和10μmol/L渥曼青黴素+5 mg/L吉西他濱組BIC RNA錶達均低于5 mg/L吉西他濱組(5.34±1.11、1.26±0.07比11.82±3.11,均P＜0.05).結論 抗癌藥物處理能明顯誘導人胰腺癌PANC-1細胞BIC RNA上調,併引起成熟miR-155上調,吉西他濱誘導的BIC RNA上調與PI3K信號通路相關.
목적 료해항암약물대인이선암세포소분자RNA 155(miR-155)급기전체B세포정합족(BIC)RNA표체적영향.방법 인이선암PANC-1세포분별급여길서타빈등항암약물처리후,실시정량RT-PCR측정BIC RNA화성숙적miR-155표체변화정황.응용린지선기순-3격매(PI3K)상관격매억제제악만청매소료해PI3K상관격매시부여BIC RNA적조절유관.결과 경항암약물처리후,PANC-1세포내BIC RNA표체현저상조,1.0、2.5、5.0、10.0 mg/L길서타빈처리후48 h BIC RNA 적표체량분별시37.1 ±4.1、29.0±5.7、21.0±7.6、40.4.±9.0,균고우대조조(1.6±1.1,균P＜0.05);처리후72 h BIC RNA표체분별위27.7 ±3.1、43.1 ±1.2、31.8±5.4、23.1±1.4,균명현고우대조조(1.0±0.1,균P＜0.05),10 mg/L 5-불뇨밀정화100 mg/L박래매소처리후48 h,BIC RNA표체분별위5.2±1.1화11.5±0.7,균고우대조조(1.7±0.7,균P＜0.05).각농도길서타빈처리후48h,PANC-1세포내miR-155수평여대조조비차이무통계학의의(P＞0.05),단처리후72 h,miR-155수평고우대조조(2.21±0.40、1.86±0.03、2.47±0.04、3.24±0.05비1.11±0.09,P＜0.05).길서타빈유도적BIC RNA상조가이피악만청매소억제,1μmol/L악만청매소+5 mg/L길서타빈조화10μmol/L악만청매소+5 mg/L길서타빈조BIC RNA표체균저우5 mg/L길서타빈조(5.34±1.11、1.26±0.07비11.82±3.11,균P＜0.05).결론 항암약물처리능명현유도인이선암PANC-1세포BIC RNA상조,병인기성숙miR-155상조,길서타빈유도적BIC RNA상조여PI3K신호통로상관.
Objective To investigate the effect of anti-cancer drugs on the expression of B-cell integration cluster (BIC) RNA/miRNA-155 in human pancreatic cancer PANC-1 cells. Methods PANC-1cells were treated with different concentrations of anti-cancer drugs. Total RNA of the treated cells were harvested and the expression levels of BIC RNA and mature miR-155 were quantified by using Taqman FAM/MGB probes on a real-time PCR system. Relative quantification was carried out using the △△Ct method. A P13K-related kinases inhibitor was used to determine whether these kinases were involved in the regulation of BIC RNA. Results The expression of BIC RNA was strongly induced by anti-cancer drugs.When PANC-1 cells were treated by gemcitabine with concentrations of 1.0, 2. 5, 5.0, 10. 0 mg/L for 48 h and 72 h, the level of BIC RNA (48 h: 37. 1 ± 4. 1,29. 0± 5.7, 21.0 ± 7.6, 40. 4 ± 9.0,72 h : 27. 7 ±3. 1,43.1± 1.2, 31.8 ± 5.4, 23. 1 ± 1.4) were signifcantly higher than that of the control (48 h : 1.6 ±1.1,72 h: 1.0 ± 0. 1, all P ＜ 0. 05 ). 5-FU (10 mg/L, 48 h) and bleomycin (100 mg/L, 48 h) also induced BIC RNA up-regulation (5. 2 ± 1.1 vs 1.7 ±0.7 ,11.5 ±0.7 vs 1.7 ±0.7, both P ＜0.05).When PANC-1 cells treated with 1.0,2. 5,5.0,10. 0 mg/L gemcitabine for 72 h, the level of miR-155(2. 21 ± 0. 40,1.86 ± 0. 03,2. 47± 0. 04,3.24 ± 0. 05 ) also higher than that of the control ( 1.11 ± 0. 09, P ＜0. 05 ) , while no change was observed when the cells only treated for 48 h. Further study showed gemcitsbine-induced BIC RNA up-regulation was inhibited by wortmannin, a specific PI3K inhibitor, the expression levels of BIC RNA of 1 μmol/L wortmannin + 5 mg/L gemcitabine group and 10 μmoL/L wortmannin + 5 mg/L gemcitabine group were 5.34 ± 1.11 and 1.26± 0. 07, lower than that of 5 mg/L gemcitabine group ( 11.82 ± 3.11, P ＜ 0. 05 ). Conclusions BIC RNA is strongly induced by anti-cancer drugs in PANC-1 cells and the levels of miR-155 also slightly increase. PI3K pathway is involved in gemcitabine-induced BIC RNA up-regulation.
