分割剂量电离辐射对卵巢癌细胞多药耐药的影响  

Effect of fractionated radiation on multidrug resistance in human ovarian cancer

作　　者：孔德娟[1] 刘晓冬[1] 梁冰[1] 贾立立[1] 马淑梅[1] 

机构地区：[1]吉林大学公共卫生学院卫生部放射生物学重点实验室,长春130021

出　　处：《中华放射医学与防护杂志》2012年第1期35-39,共5页Chinese Journal of Radiological Medicine and Protection

基　　金：国家高校博士点基金（20100061110070）;吉林省卫生厅基金（20082023）

摘　　要：目的研究不同分割剂量电离辐射方案对卵巢癌细胞多药耐药性的影响。方法采用卵巢癌亲本细胞SKOV3及其耐药细胞株SKVCR，分别进行假照射、单次照射（10Gy）、常规分割照射（2Gy×5）和超分割照射（1Gy×2×5）。MTT方法检测细胞对4种化疗药物硫酸长春新碱（vineristlne，VCR）、依托泊苷（etoposide，VP—16）、盐酸吡柔比星（pirarubicin，THP）和顺铂（cisplatin，DDP）敏感性的变化。Westernblot检测P-gp蛋白表达量。结果与SKOV3相比，SKVCR倍增时间增加为1．8倍，P-gp糖蛋白表达增高，4种药物对SKVCR的，IC50浓度明显增加（P〈0．05）。在SKOV3中，与假照组相比，单次照射后细胞对THP、DDP药敏性降低，常规分割照射后细胞对VCR、THP、VP-16药敏性降低，超分割照射使VP-16药敏性降低；在SKVCR中，与假照组相比，3个照射组对VCR、VP．16的药敏性增高，对DDP的药敏性无明显改变，单次和分割照射均可降低P-gp表达。结论单次、分割和超分割照射在SKOV3亲本细胞中诱导多药耐药，在耐药株SKVCR中逆转对VCR、VP-16的耐药性。Objective To investigate the effect of different subtypes of fractionated doses on multidrug resistance in ovarian cancer cells. Methods The human ovarian cancer cell lines SKOV3 and its drug-resistant subtype SKVCR were divided into four groups i. e. , sham-irradiated, single dose （10 Gy）, fractionated dose （2 Gy ×5 ） and muhi-fractionated dose （1 Gy × 2 × 5）. Cell sensitivity to vincristine（VCR）, etoposide （ VP-16）, pirarubicin （THP） and cisplatin （DDP） was measured by MTT assay. Western blot was applied to detect the expression of P-gp after irradiation. Results The doubling time of SKVCR was about 1.8-fold of that of SKOV3 cells. P-gp was expressed in SKVCR but not in SKOV3. IC5o values of SKVCR were higher than those of SKOV3. To SKOV3 cells, single dose irradiation decreased cell sensitivity to THP and DDP and fractionated irradiation decreased cell sensitivity to VCR, THP and VP-16. Multi-fractionated irradiation decreased cell sensitivity to VP-16. In SKVCR cells, all these irradiation treatments increased cell sensitivity to VCR and VP-16 but not to DDP. In addition, single and fractionated irradiation decreased P-gp expression in SKVCR cells. Conclusions Single, fractionated and multi-fractionated radiation induced chemotherapy resistance in SKOV3 cells, while reversed drug resistance to VCR and VP-16 in SKVCR cells.

关 键 词：多药耐药 分割照射 卵巢癌 P-糖蛋白 

分 类 号：R737.31[医药卫生—肿瘤]