全反式维甲酸提高人结肠癌细胞亚株SW480/M5对奥沙利铂敏感性  

All-trans retinoic acid-induced drug sensitivity of oxaliplatin in human colorectal cancer cell sub-line SW480/M5

作　　者：吕会增[1] 魏波[2] 郑宗珩[2] 陈新岐[1] 叶小勇[1] 卫洪波[2] 

机构地区：[1]广州医学院第五附属医院普外科,510700 [2]中山大学附属第三医院胃肠外科

出　　处：《消化肿瘤杂志（电子版）》2012年第3期170-175,共6页Journal of Digestive Oncology(Electronic Version)

基　　金：广州医学院博士启动基金资助项目(编号20100136)

摘　　要：目的探讨全反式维甲酸(all-trans retinoicacid,ATRA)提高人结肠癌细胞亚株SW480/M5对奥沙利铂(oxaliplatin,L-OHP)敏感性的可能机制。方法 MTT法筛选ATRA和L-OHP实验浓度。流式细胞仪检测ATRA对肿瘤细胞周期影响。分别用ATRA、L-OHP、ATRA联合L-OHP作用SW480/M5细胞,MTT法检测药物对肿瘤细胞抑制率,流式细胞仪检测肿瘤细胞周期及凋亡率,原子光谱吸收仪检测肿瘤细胞DNA含铂(Pt)量。结果 L-OHP抑制SW480/M5细胞增殖的GI50为58.0mg/L,主要阻滞肿瘤细胞在S和G2/M期。ATRA8.0μmol/L作用24小时后,G1期细胞减少,S期细胞增多;作用72小时后,S期和G2/M期细胞增加并明显抑制肿瘤细胞增殖。8.0μmol/LATRA作用至48小时后联合L-OHP,两药联合由相加作用转变为协同作用;联合用药后S期和G2/M期细胞明显增多,细胞DNA含Pt量显著增加,呈时效依赖性。相对于单独用药,联合用药并不上调肿瘤细胞凋亡率。结论 ATRA通过改变SW480/M5细胞周期和提高细胞DNA含Pt量,明显增加肿瘤细胞对L-OHP敏感性。Objective To investigate the role of ATRA (all-trans retinoic acid) in inducing drug sensitivity of oxaliplatin (L-OHP) in human colorectal cancer cell sub-line SW480/M5. Methods The drug concentrations of ATRA or L-OHP in SW480/M5 cells were determined by MTT screen assay. SW480/M5 cell cycle changes induced by ATRA were detected by flow cytometry (FCM). ATRA, L-OHP,or ATRA combined with L-OHP were respectively added in SW480/M5 cell cultures. Growth inhibitory activity against SW480/M5 cells was determined by MTT assay. Cell cycle and apoptosis induced by different drugs were assessed by FCM. Pt-DNA adducts in SW480/M5 cells were determined by atomic absorption spectrometer. Results The GI 50 of L-OHP to SW480 / M5 cells was 58.0 mg/L , and L-OHP mainly blocked SW480/M5 cells in S-and G2/M phases. ATRA at 8.0 μmo/L had significant growth inhibitory activity against SW480/M5 cells after 72 h ATRA treatment. The percentage of the cells in G1 phase decreased and the cells in S-phase increased after 24 h ATRA treatment , while the percentages of the cells in S-and G2/M phases increased significantly after 72 h treatment. The role of L-OHP combined with ATRA in SW480/M5 cells was changed gradually from addition to synergistic effect from 24 h to 48 h after ATRA treatment. The percentage of cells in S-and G2/M phases treatedwith the combined drugs was higher than that treated with simple L-OHP. The apoptosis rate induced by the combined drugs was the same as that by simple L-OHP. Compared with simple L-OHP , the combined drugs resulted in more Pt-DNA adducts in a time-dependent manner. Conclusion ATRA can induce drug sensitivity of L-OHP by changing cell cycle and increasing Pt-DNA adducts in human colorectal cancer SW480/M5 cells.

关 键 词：全反式维甲酸 奥沙利铂 人结肠癌细胞亚株SW480/M5 联合用药 药物敏感性 

分 类 号：R735.35[医药卫生—肿瘤]