奥曲肽逆转人胰腺癌细胞多药耐药机制的初步研究

目的：探讨生长抑素类似物奥曲肽对人胰腺癌细胞BxPC-3多药耐药现象的逆转作用及其机理,为临床应用奥曲肽提高胰腺癌化疗疗效提供实验依据。方法：应用不同浓度的奥曲肽（0-1.6μg/ml）联合化疗药物顺铂、表阿霉素、氟尿嘧啶、吉西他滨共同处理稳定表达SSTR2的胰腺癌细胞BxPC-3-SSTR2,CCK-8比色法测定奥曲肽处理前后各化疗药物的IC50值,判断奥曲肽对胰腺癌多药耐药的逆转。Real-timePCR法检测SSTR2基因转染前后及奥曲肽处理前后的胰腺癌细胞中MDR1、MRP2、LRP基因表达。结果：奥曲肽可以显著降低顺铂、表阿霉素、氟尿嘧啶和吉西他滨的IC50值（P〈0.05）,并且这种作用呈剂量依赖性。胰腺癌细胞株BxPC-3在转染SSTR2基因后,细胞中MDR1、MRP2、LRP基因的表达分别下调57%、47%和56%（P〈0.01）;而转染后的胰腺癌细胞经过1.6μg/ml奥曲肽作用48h后,其所表达的MDR1、MRP2、LRP基因出现进一步的下调,分别下降88%、73%和87%（P〈0.01）。结论：生长抑素类似物奥曲肽可逆转胰腺癌细胞的多药耐药,其机制可能与降低胰腺癌细胞中MDR1、MRP、LRP基因的表达,使胰腺癌细胞内细胞毒性药物浓度增加有关。

Mechanism of octreotide reversing multidrug resistance in human pancreatic cancer cell line BxPC-3

Objective： Somatostatin （SST） and somatostantin analogue （SSA） have antineoplasmic activity, and can reverse multidrug resistance of many tumors. This study was to investigate the reverse multidrug resistance in human pancreatic cancer cell line BxPC-3 of somatostatin analogue octreotide and its mechanism. Methods： BxPC-3 and BxPC-3-SSTR2 cells were processed by different concentration （0-1.6μg/ml） octreotide combining with cytotoxic drug of cisplatin, epirubicin, fluracil and gemcitabine. The IC50 of each chemotherapeutic drug was tested by CCK-8 chromatometry before and after processing. The variation of the expression of MDR1, MRP2, LRP gene in pancreatic cancer cells were detected before and after being tranfected with SSTR2 gene and processed with octreotide through Real-time PCR. Results： Octreotide significantly reduced the IC50 of cisplatin, epirubicin, fluracil and gemcitabine（P0.05）with characteristics of dose- dependent. The expression of MDR1,MRP2,LRP gene in BxPC-3 decreased by 57%,47% and 56%（P0.01）respectively when SSTR2 gene was transfected, and they were further down-regulated by 88%,73% and 87%（P0.01）respectively after the transfected cells were processed by octreotide 1.6μg/ml for 48h. Conclusion： Octreotide can reverse the multidrug resistance of human pacreatic cancer cells. The mechanism may be down-regulated the expression of MDR1, MRP, LRP gene in pancreatic cancer cells.