摘要
目的探讨阿霉素(ADM)加热化疗对人肝癌细胞BEL7402(以下简称BEL7402细胞)及其耐药株BEL7402/ADM细胞(以下简称BEL7402/ADM细胞)的凋亡诱导作用。方法以体外培养的人肝癌细胞BEL7402和BEL7402/ADM细胞为研究对象,采用水浴加温法,观察单纯热疗、单纯ADM化疗与热化疗对细胞凋亡的影响。用AnnexinV-FITC和PI双染色流式细胞仪检测细胞凋亡;采用流式细胞技术检测加热对BEL7402细胞和BEL7402/ADM细胞胞内ADM浓度和细胞膜上P糖蛋白(P-gp),多药耐药性相关蛋白(MRP)的影响。结果热化疗组细胞凋亡率(%)显著高于单纯热疗、单纯ADM化疗组的同种细胞[BEL7402细胞:(79.21±0.54)vs(16.67±1.03),(48.91±0.05),P均<0.05;BEL7402/ADM细胞:(75.42±0.16)vs(14.79±0.61),(23.78±0.04),P均<0.05]。热化疗组细胞内ADM浓度显著高于单纯化疗组的同种细胞(P<0.05)。热化疗组和单纯热疗组细胞膜上P-gp、MRP的表达率显著低于单纯化疗组的同种细胞(P<0.05)。结论加热可能通过抑制细胞膜上P-gp、MRP的表达,从而提高BEL7402细胞及BEL7402/ADM细胞对ADM诱导凋亡作用的敏感性。
Objective To comparatively study the apoptosis-inducing effects of chemotherapy and thermochemotherapy of ADM on human hepatocellular carcinoma cell line （BEL7402） and human multidrug-resistant hepatocellular carcinoma cell line （BEL7402/ADM）. Methods BEL7402 and BEL7402/ADM cells were both treated by ADM and ADM in combination with warm water bath. The cell apoptosis was detected by flow cytometry （Annexin V-FITC-PI assay）; the intracellular concentration of ADM of BEL7402 and BEL7402/ADM cells were detected by flow cytometry; the expression of P-gp and MRP on the cell surface were determined by indirect fluorescence staining and flow cytometry analysis. Results Cell apoptosis rate of thermochemotherapy group is significantly higher than hyperthermia group and chemotherapy group [BEL7402 cell： （79.21 ± 0.54） vs （16.67 ± 1.03）, （48 ： 91 ± 0.05）, respectively, P 〈 0.05 ; BEL7402/ADM cell： （ 75.42 ± 0.16 ） vs （ 14.79 ± 0.61 ）, （ 23.78 ± 0.04 ）, respectively, P 〈 0.05].Intracellular concentration of ADM in thermochemotherapy group is significantly higher than chemotherapy group （P 〈 0.05）.Expression of P-gp and MRP on the cell surface in thermochemotherapy and hyperthermia group is significantly lower than chemotherapy group and control group （P 〈 0.05）. Conclusion Hyperthermia can increase the sensitivity of BEL7402 and BEL7402/ADM cells to ADM-induced apoptosis by down-regulating he expression of P-gp and MRP on the cell surface.
出处
《实用癌症杂志》
2006年第6期570-572,593,共4页
The Practical Journal of Cancer
